Статті в журналах з теми "Tissuee inhibitors of metalloproteinase"
Щоб переглянути інші типи публікацій з цієї теми, перейдіть за посиланням: Tissuee inhibitors of metalloproteinase.
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 статей у журналах для дослідження на тему "Tissuee inhibitors of metalloproteinase".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте статті в журналах для різних дисциплін та оформлюйте правильно вашу бібліографію.
1
Hsia, Tain-Yen, Jeremy M. Ringewald, Robert E. Stroud, Nadia Roessler, Nidhi Kumar, Scott T. Reeves, and Francis G. Spinale. "Plasma profiling determinants of matrix homeostasis in paediatric dilated cardiomyopathy." Cardiology in the Young 21, no. 1 (October 27, 2010): 52–61. http://dx.doi.org/10.1017/s1047951110001381.
Повний текст джерелаАнотація:
AbstractObjectiveDilated cardiomyopathy is an important cause of cardiac failure in both children and adults, but is more progressive in children. In adult dilated cardiomyopathy, left ventricular remodelling is associated with changes in the plasma levels of matrix metalloproteinases and tissue inhibitor of metalloproteinases. Plasma matrix metalloproteinases and tissue inhibitors of metalloproteinase changes in paediatric dilated cardiomyopathy have not been examined. This study developed a low blood volume, high-sensitivity assay to test the hypothesis that unique and differential plasma matrix metalloproteinases and tissue inhibitors of metalloproteinase profile exist in patients with paediatric dilated cardiomyopathy.Methods/resultsA systemic blood sample (1 millilitre) was obtained from seven children aged 8 plus or minus 7 years with dilated cardiomyopathy and 26 age-matched normal volunteers. Using a high-throughput multiplex suspension immunoassay, plasma levels were quantified for collagenases (matrix metalloproteinase-8), gelatinases (matrix metalloproteinase-2 and -9), lysins (matrix metalloproteinase-3 and -7), and tissue inhibitor of metalloproteinases-1, -2, and -4. The matrix metalloproteinase to tissue inhibitors of metalloproteinases ratios were also calculated. The plasma matrix metalloproteinase-2, -7, -8, and -9 levels were increased by greater than twofold in patients with dilated cardiomyopathy than normal patients (with p less than 0.05). Patients with dilated cardiomyopathy also had significantly higher tissue inhibitors of metalloproteinases-1 and -4 (298% and 230%; with p less than 0.05).ConclusionsThese unique findings show that a specific plasma matrix metalloproteinase/tissue inhibitor of metalloproteinase profile occurs in paediatric dilated cardiomyopathy when compared to the cases of normal children. These distinct differences in the determinants of myocardial matrix structure and function may contribute to the natural history of dilated cardiomyopathy in children and may provide a novel biomarker platform in paediatric dilated cardiomyopathy.
2
COWELL, Susan, Vera KNÄUPER, Margaret L. STEWART, Marie-Pia D'ORTHO, Heather STANTON, Rosalind M. HEMBRY, Carlos LÓPEZ-OTÍN, John J. REYNOLDS, and Gillian MURPHY. "Induction of matrix metalloproteinase activation cascades based on membrane-type 1 matrix metalloproteinase: associated activation of gelatinase A, gelatinase B and collagenase 3." Biochemical Journal 331, no. 2 (April 15, 1998): 453–58. http://dx.doi.org/10.1042/bj3310453.
Повний текст джерелаАнотація:
SW1353 chondrosarcoma cells cultured in the presence of interleukin-1, concanavalin A or PMA secreted procollagenase 3 (matrix metalloproteinase-13). The enzyme was detected in the culture medium by Western blotting using a specific polyclonal antibody raised against recombinant human procollagenase 3. Oncostatin M enhanced the interleukin-1-induced production of procollagenase 3, whereas interleukin-4 decreased procollagenase 3 synthesis. The enzyme was latent except when the cells had been treated with concanavalin A, when a processed form of 48 kDa, which corresponds to the active form, was found in the culture medium and collagenolytic activity was detected by degradation of 14C-labelled type I collagen. The concanavalin A-induced activation of procollagenase 3 coincided with the processing of progelatinase A (matrix metalloproteinase-2) by the cells, as measured by gelatin zymography. In addition, progelatinase B (matrix metalloproteinase-9) was activated when gelatinase A and collagenase 3 were in their active forms. Concanavalin A treatment of SW1353 cells increased the amount of membrane-type-1 matrix metalloproteinase protein in the cell membranes, suggesting that this membrane-bound enzyme participates in an activation cascade involving collagenase 3 and the gelatinases. This cascade was effectively inhibited by tissue inhibitors of metalloproteinases-2 and -3. Tissue inhibitor of metalloproteinases-1, which is a much weaker inhibitor of membrane-type 1 matrix metalloproteinase than tissue inhibitors of metalloproteinases-2 and -3 [Will, Atkinson, Butler, Smith and Murphy (1996) J. Biol. Chem. 271, 17119–17123], was a weaker inhibitor of the activation cascade.
3
Adamson, R. E., and F. R. Hall. "Matrix metalloproteinases mediate the metastatic phenotype ofTheileria annulata-transformed cells." Parasitology 113, no. 5 (November 1996): 449–55. http://dx.doi.org/10.1017/s0031182000081518.
Повний текст джерелаАнотація:
SUMMARYTheileria annulatainfects and reversibly transforms bovine leucocytes. The parasite-transformed cells are immortalized, metastatic and express a number of metalloproteinases including matrix metalloproteinase 9 which they secrete. All the metalloproteinases observed on substrate gels are inhibited by tissue inhibitor of metalloproteinase 1 and 4 synthetic inhibitors BB94, GM6001, BRL29808AI and Ro31–4724. We have adapted anin vitroassay for metastatic behaviour that measures the ability of parasitized cells to cross reconstituted basement membrane, Matrigel™. Using this we demonstrated that macroschizont-infected cells are invasivein vitroand that their invasive properties can be almost eliminated by the same specific inhibitors of metalloproteinases as used in the substrate gels. This demonstrates that the metastatic behaviour of the infected cells is due in part to metalloproteinase activity and strongly suggests a role for the metalloproteinases we observed on gels. This is further supported by the fact that an attenuated vaccine line which shows much reduced metalloproteinase activity also exhibits a marked reduction in metastatic behaviour. We suggest that these metalloproteinases are virulence factors mediating some pathological features of the disease and their loss in the vaccine line could provide an explanation for attenuation.
4
Lauer-Fields, Janelle L., Mare Cudic, Shuo Wei, Frank Mari, Gregg B. Fields, and Keith Brew. "Engineered Sarafotoxins as Tissue Inhibitor of Metalloproteinases-like Matrix Metalloproteinase Inhibitors." Journal of Biological Chemistry 282, no. 37 (July 10, 2007): 26948–55. http://dx.doi.org/10.1074/jbc.m611612200.
Повний текст джерела
5
Nagase, Hideaki, and Keith Brew. "Designing TIMP (tissue inhibitor of metalloproteinases) variants that are selective metalloproteinase inhibitors." Biochemical Society Symposia 70 (September 1, 2003): 201–12. http://dx.doi.org/10.1042/bss0700201.
Повний текст джерелаАнотація:
The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs), enzymes that play central roles in the degradation of extracellular matrix components. The balance between MMPs and TIMPs is important in the maintenance of tissues, and its disruption affects tissue homoeostasis. Four related TIMPs (TIMP-1 to TIMP-4) can each form a complex with MMPs in a 1:1 stoichiometry with high affinity, but their inhibitory activities towards different MMPs are not particularly selective. The three-dimensional structures of TIMP-MMP complexes reveal that TIMPs have an extended ridge structure that slots into the active site of MMPs. Mutation of three separate residues in the ridge, at positions 2, 4 and 68 in the amino acid sequence of the N-terminal inhibitory domain of TIMP-1 (N-TIMP-1), separately and in combination has produced N-TIMP-1 variants with higher binding affinity and specificity for individual MMPs. TIMP-3 is unique in that it inhibits not only MMPs, but also several ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin motifs) metalloproteinases. Inhibition of the latter groups of metalloproteinases, as exemplified with ADAMTS-4 (aggrecanase 1), requires additional structural elements in TIMP-3 that have not yet been identified. Knowledge of the structural basis of the inhibitory action of TIMPs will facilitate the design of selective TIMP variants for investigating the biological roles of specific MMPs and for developing therapeutic interventions for MMP-associated diseases.
6
Curry, V. A., I. M. Clark, H. Bigg, and T. E. Cawston. "Large inhibitor of metalloproteinases (LIMP) contains tissue inhibitor of metalloproteinases (TIMP)-2 bound to 72,000-Mr progelatinase." Biochemical Journal 285, no. 1 (July 1, 1992): 143–47. http://dx.doi.org/10.1042/bj2850143.
Повний текст джерелаАнотація:
Connective-tissue cells in culture produce a family of metalloproteinases which, once activated, can degrade all the components of the extracellular matrix. These potent enzymes are all inhibited by the tissue inhibitor of metalloproteinases (TIMP), and it was thought that this inhibitor was solely responsible for the inhibition of these enzymes within connective tissue. However, other inhibitors have recently been described, including large inhibitor of metalloproteinases (LIMP) present in the culture medium of human foetal lung fibroblasts. Here we show that a large proportion of the inhibitory activity of LIMP consists of 72,000-M(r)-progelatinase bound to TIMP-2, a recently discovered low-M(r) metalloproteinase inhibitor closely related to TIMP. The physiological implications of the secretion of a complex of 72,000-M(r) progelatinase and TIMP-2 are discussed, and the separation of the complex in 6 M-urea is described.
7
Kalinkina, T. V., N. V. Lareva, and M. V. Chistyakova. "Some indicators of left ventricular dysfunction in hypertensive patients, depending on the level of matrix metalloproteinases and tissue inhibitors of metalloproteinase-1." Kazan medical journal 102, no. 6 (December 13, 2021): 815–20. http://dx.doi.org/10.17816/kmj2021-815.
Повний текст джерелаАнотація:
Aim. To study the level of matrix metalloproteinases-1 and -2, and tissue inhibitor of metalloproteinases-1, the indicator of left ventricular myocardial deformation in patients with stage 12 hypertension.
Methods. 114 patients (40 women and 74 men) with hypertension of 12 stages observed in the cardiology Department of the Road clinical hospital Chita II were examined. The median age was 428.3 years. Left ventriclular diastolic function was studied by using tissue Doppler imaging in apical four-chamber views. Serum matrix metalloproteinase-1, matrix metalloproteinase-2, and tissue inhibitor of metalloproteinases-1 levels were measured in all patients on automated immunoassay analyzers using ready-to-use ELISA kits.
Results. An increase in serum levels of matrix metalloproteinases-1 and -2 in the group of patients with hypertension and diastolic dysfunction by 46 and 47%, respectively, was found against increased levels of serum tissue inhibitor of metalloproteinase-1 (р=0.049). In patients with diastole dysfunction, myocardial global longitudinal strain was decreased in was observed by 22.8% compared with patients without diastole dysfunction (p 0.05). The analysis revealed a moderate negative relationship between left ventricular global longitudinal strain and the serum levels of metalloproteinases-2 (r=0.64, p 0.05).
Conclusion. In patients with hypertension and left ventricular diastolic dysfunction, a decrease in left ventricular global longitudinal strain is associated with the serum level of matrix metalloproteinase-2; a tissue inhibitor of metalloproteinases-1 is unrelated to left ventricular global myocardial strain.
8
Inzitari, Domenico, Betti Giusti, Patrizia Nencini, Anna Maria Gori, Mascia Nesi, Vanessa Palumbo, Benedetta Piccardi, et al. "MMP9 Variation After Thrombolysis Is Associated With Hemorrhagic Transformation of Lesion and Death." Stroke 44, no. 10 (October 2013): 2901–3. http://dx.doi.org/10.1161/strokeaha.113.002274.
Повний текст джерелаАнотація:
Background and Purpose— Experimentally, matrix metalloproteinases (MMPs) play a detrimental role related to hemorrhagic transformation and severity of an ischemic brain lesion. Tissue-type plasminogen activator (tPA) enhances such effects. This study aimed to expand clinical evidence in this connection. Methods— We measured MMPs 1, 2, 3, 7, 8, 9, and tissue inhibitors of metalloproteinases 1, 2, 4 circulating level in blood taken before and 24 hours after tPA from 327 patients (mean age, 68.9±12.1 years; median National Institutes of Health Stroke Scale, 11) with acute ischemic stroke. Delta median values ([24 hours post tPA–pre tPA]/pre tPA) of each MMP or tissue inhibitors of metalloproteinase were analyzed across subgroups of patients undergoing symptomatic intracerebral hemorrhage, 3-month death, or 3-month modified Rankin Scale score 3 to 6. Results— Adjusting for major clinical determinants, only matrix metalloproteinase-9 variation proved independently associated with death (odds ratio [95% confidence interval], 1.58 [1.11–2.26]; P =0.045) or symptomatic intracerebral hemorrhage (odds ratio [95% confidence interval], 1.40 [1.02–1.92]; P =0.049). Both matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-4 changes were correlated with baseline, 24 hours, and 7 days National Institutes of Health Stroke Scale (Spearman P from <0.001 to 0.040). Conclusions— Our clinical evidence corroborates the detrimental role of matrix metalloproteinase-9 during ischemic stroke treated with thrombolysis, and prompts clinical trials testing agents antagonizing its effects.
9
Thomas, Noel Vinay, and Se-Kwon Kim. "Metalloproteinase Inhibitors: Status and Scope from Marine Organisms." Biochemistry Research International 2010 (2010): 1–10. http://dx.doi.org/10.1155/2010/845975.
Повний текст джерелаАнотація:
Marine environment has been the source of diverse life forms that produce different biologically active compounds. Marine organisms are consistently contributing with unparalleled bioactive compounds that have profound applications in nutraceuticals, cosmeceuticals, and pharmaceuticals. In this process, screening of natural products from marine organisms that could potentially inhibit the expression of metalloproteinases has gained a huge popularity, which became a hot field of research in life sciences. Metalloproteinases, especially, matrix metalloproteinases (MMPs) are a class of structurally similar enzymes that contribute to the extracellular matrix degradation and play major role in normal and pathological tissue remodeling. Imbalance in the expression of MMPs leads to severe pathological condition that could initiate cardiac, cartilage, and cancer-related diseases. Three decades of endeavor for designing potent matrix metalloproteinase inhibitory substances (MMPIs) with many not making upto final clinical trials seek new resources for devising MMPIs. Umpteen number of medicinally valuable compounds being reported from marine organisms, which encourage current researchers to screen potent MMPIs from marine organisms. In this paper, we have made an attempt to report the metalloproteinase inhibiting substances from various marine organisms.
10
Librach, C. L., Z. Werb, M. L. Fitzgerald, K. Chiu, N. M. Corwin, R. A. Esteves, D. Grobelny, R. Galardy, C. H. Damsky, and S. J. Fisher. "92-kD type IV collagenase mediates invasion of human cytotrophoblasts." Journal of Cell Biology 113, no. 2 (April 15, 1991): 437–49. http://dx.doi.org/10.1083/jcb.113.2.437.
Повний текст джерелаАнотація:
The specialized interaction between embryonic and maternal tissues is unique to mammalian development. This interaction begins with invasion of the uterus by the first differentiated embryonic cells, the trophoblasts, and culminates in formation of the placenta. The transient tumor-like behavior of cytotrophoblasts, which peaks early in pregnancy, is developmentally regulated. Likewise, in culture only early-gestation human cytotrophoblasts invade a basement membrane-like substrate. These invasive cells synthesize both metalloproteinases and urokinase-type plasminogen activator. Metalloproteinase inhibitors and a function-perturbing antibody specific for the 92-kD type IV collagen-degrading metalloproteinase completely inhibited cytotrophoblast invasion, whereas inhibitors of the plasminogen activator system had only a partial (20-40%) inhibitory effect. We conclude that the 92-kD type IV collagenase is critical for cytotrophoblast invasion.
11
Hansell, Elizabeth J., Steven M. Frisch, Patrice Tremble, John P. Murnane, and Zena Werb. "Simian virus 40 transformation alters the actin cytoskeleton, expression of matrix metalloproteinases and inhibitors of metalloproteinases, and invasive behavior of normal and ataxia-telangiectasia human skin fibroblasts." Biochemistry and Cell Biology 73, no. 7-8 (July 1, 1995): 373–89. http://dx.doi.org/10.1139/o95-045.
Повний текст джерелаАнотація:
Alterations in the actin cytoskeleton of normal cells result in changes in cell shape and adhesiveness and induce expression of matrix-degrading matrix metalloproteinases. We examined the effect of simian virus 40 transformation of normal and ataxia-telangiectasia human skin fibroblasts, a process that produces actin reorganization, altered cell morphology, and altered cell behavior, on expression of genes of the matrix metalloproteinase and tissue inhibitor of metalloproteinases gene families. Simian virus 40 transformation induced collagenase-1 gene expression; in contrast, stromelysin-1, 72-kDa gelatinase (gelatinase A), tissue inhibitor of metalloproteinases-1, and tissue inhibitor of metalloproteinases-2 genes were repressed. Transformation also altered the response of the fibroblasts to 12-O-tetradecanoylphorbol-13-acetate. Collagenase mRNA was induced in 12-O-tetradecanoylphorbol-13-acetate treated transformed cells up to 50-fold more than in untreated transformed cells or in 12-O-tetradecanoylphorbol-13-acetate treated untransformed parent cells. In contrast, 12-O-tetradecanoylphorbol-13-acetate did not overcome the attenuated expression of stromelysin-1 in the simian virus 40 transformants. In addition, 92-kDa gelatinase (gelatinase B) was induced by 12-O-tetradecanoylphorbol-13-acetate only in the simian virus 40 transformants. The responses of gelatinase A and tissue inhibitor of metalloproteinases-1 to 12-O-tetradecanoylphorbol-13-acetate were unchanged. The pattern of altered proteinase expression after transformation was accompanied by a phenotypic alteration in cell invasion. The simian virus 40 transformants exhibited enhanced invasiveness through a basement-membrane-like matrix. These data demonstrate that enhanced invasiveness in simian virus 40 transformed cells is accompanied by changes in actin organization and expression of proteinases and inhibitors, as well as in the balance between proteinases and inhibitors in favor of proteinases.Key words: actin cytoskeleton, collagenase, metalloproteinase, tissue inhibitor of metalloproteinases, SV40 transformation, ataxia-telangiectasia.
12
Li, Qinglei, Fermin Jimenez-Krassel, Yasuhiro Kobayashi, James J. Ireland, and George W. Smith. "Effect of intrafollicular indomethacin injection on gonadotropin surge-induced expression of select extracellular matrix degrading enzymes and their inhibitors in bovine preovulatory follicles." Reproduction 131, no. 3 (March 2006): 533–43. http://dx.doi.org/10.1530/rep.1.00926.
Повний текст джерелаАнотація:
A growing body of evidence supports an obligatory role for intrafollicular prostanoids in the mechanism of ovulation. However, the prostanoid-dependent mediators of the follicular extracellular matrix degradation required for ovulation are unknown. The objectives of this study were to determine the cellular compartment(s) in which the gonadotropin surge-induced regulation of select extracellular matrix degrading enzymes and their cognate inhibitors occurs in bovine preovulatory follicles, and to test whether such regulation is blocked by intrafollicular administration of the prostanoid synthesis and ovulation inhibitor, indomethacin (INDO). Follicular fluid prostaglandin E2concentrations were elevated in diluent-treated follicles before ovulation (24 h after GnRH injection), but the increase was blocked in INDO-treated follicles. Real-time PCR analysis revealed the specific follicular cell types where gonadotropin surge-induced increases in mRNA abundance for members of the matrix metalloproteinase/tissue inhibitor of metalloproteinase and plasminogen activator families occurred. INDO treatment increased thecal cell mRNA for tissue inhibitor of metalloproteinase-4 and its protein abundance in the apex of preovulatory follicles before ovulation, but suppressed granulosal cell mRNA and activity for tissue plasminogen activator in follicular fluid and the follicle apex. Plasmin activity was also suppressed in the follicular fluid of INDO-treated follicles. Effects of INDO injection on select matrix metalloproteinases were not observed. The results suggest that gonadotropin surge-induced regulation of tissue inhibitor of metalloproteinase-4 and tissue plasminogen activator may be prostanoid dependent, and support a potential role for increased tissue plasminogen activator expression and decreased tissue inhibitor of metalloproteinase-4 expression in the mechanism of ovulation.
13
Armstrong, David G., and Edward B. Jude. "The Role of Matrix Metalloproteinases in Wound Healing." Journal of the American Podiatric Medical Association 92, no. 1 (January 1, 2002): 12–18. http://dx.doi.org/10.7547/87507315-92-1-12.
Повний текст джерелаАнотація:
The structure, classification, function, and regulation of matrix metalloproteinases in normal and abnormal wound healing is discussed. Results from key studies suggest that neutrophil-derived matrix metalloproteinase 8 (MMP-8) is the predominant collagenase present in normal healing wounds, and that overexpression and activation of this collagenase may be involved in the pathogenesis of nonhealing chronic leg ulcers. Excessive collagenolytic activity in these chronic wounds is possible because of the reduced levels of tissue inhibitor metalloproteinase 1 (TIMP-1). However, until recently, there have been no studies evaluating levels of matrix metalloproteinase or tissue inhibitors of metalloproteinase activity in chronic diabetic foot wounds. Improving basic knowledge and pharmaceutical intervention in this area ultimately may help clinicians identify and proactively intervene in an effort to prevent normal wounds from becoming chronic. This may prevent the high prevalence of morbidity associated with this significant health problem. (J Am Podiatr Med Assoc 92(1): 12-18, 2002)
14
Ismael, May, Lubna Rasuol, and Yasir Qaddoori. "Investigation of the relationship between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase with SARS CoV-2 infections." Journal of Advanced Biotechnology and Experimental Therapeutics 6, no. 1 (2023): 35. http://dx.doi.org/10.5455/jabet.2023.d104.
Повний текст джерелаАнотація:
SARS-CoV-2 stands for severe acute respiratory syndrome coronavirus 2 which is the causative agent of spreading coronavirus disease 2019 that is known as COVID-19 pandemic, the disease leads to severe acute respiratory illness. Matrix metalloproteinases- 9 (MMP-9) plays several important physiological functions. This enzyme could also be implicated in the "cytokine storm" in some way, which may represent one of the possible scianrios during coronavirus infection, in addition to its role in the mechanism of lung fibrosis on molecular basis.. The tissue inhibitors of metalloproteinase (TIMPs) are well characterized for controlling the activity of MMPs in extracellular matrix remodeling. They also considered as signaling molecules analogous to cytokine activities in the sense of impact on a variety of biological processes; this study aimed to investigate the link between each of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), and COVID19 disease. A total of 58 COVID-19 patients and 30 apparently healthy adults were enrolled in this study. The ORF1ab, E. and N genes of SARS-CoV-2 were detected using Multiplex real-time PCR, while the ELISA technique was used to estimate the level of serum matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and CRP. The study results demonstrated higher concentrations of matrix metalloproteinase-9 (MMP-9) in COVID-19 patients compared with controls, with non-significant differences obtained. Unlike, tissue inhibitor of metalloproteinase-1 (TIMP-1), showed considerably higher levels in the patients group than in controls, with high significant differences according to the data statistical analysis (p≤0.001). In a conclusion, the rising trend of TIMP-1 in COVID patients could be promising to suggest serum tissue inhibitor of metalloproteinase-1 (TIMP-1) as an applicable biomarker in the diagnosis of COVID‐19.
15
Adler, R. R., C. A. Brenner, and Z. Werb. "Expression of extracellular matrix-degrading metalloproteinases and metalloproteinase inhibitors is developmentally regulated during endoderm differentiation of embryonal carcinoma cells." Development 110, no. 1 (September 1, 1990): 211–20. http://dx.doi.org/10.1242/dev.110.1.211.
Повний текст джерелаАнотація:
The differentiation of F9 and PSA-1 embryonal carcinoma cells to embryoid bodies composed of a mixture of parietal and visceral endoderm was accompanied by changes in their secretion of metalloproteinases. Differentiation was induced by retinoic acid and dibutyryl cyclic AMP (for F9 cells) or by removing cells from a substrate of feeder cells to alter cell-cell interaction and adhesion (for PSA-1 cells). The embryoid bodies attached to gelatin-coated dishes, and the parietal endoderm cells spread out over the matrix. The differentiated cells secreted specific gelatin- and casein-degrading proteinases, including enzymes that comigrated with proenzyme forms of collagenase and stromelysin. Total proteinase activity as well as specific collagenase activity increased with the time of differentiation. All of the gelatin- and casein-degrading proteinases detectable by substrate gel zymography were inhibited by inhibitors of metalloproteinases but not by inhibitors of serine or cysteine proteinases, indicating that they were metalloproteinases. Both cell lines showed increased collagenolytic activity, which was activated by treatment with plasmin. In addition, both cell lines showed increased secretion of specific metalloproteinase inhibitors, including tissue inhibitor of metalloproteinases, with differentiation. Analysis of mRNA from undifferentiated and differentiated F9 cells by RNA blot analysis or reverse transcription coupled with the polymerase chain reaction showed that increased expression of genes for collagenase, stromelysin and tissue inhibitor of metalloproteinases is associated with differentiation of these cells. These results suggest that the expression of extracellular matrix-degrading metalloproteinases and their inhibitors is developmentally regulated during the differentiation and spreading of the parietal endoderm.
16
Raeeszadeh-Sarmazdeh, Maryam, Linh Do, and Brianne Hritz. "Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics." Cells 9, no. 5 (May 25, 2020): 1313. http://dx.doi.org/10.3390/cells9051313.
Повний текст джерелаАнотація:
The metalloproteinase (MP) family of zinc-dependent proteases, including matrix metalloproteinases (MMPs), a disintegrin and metalloproteases (ADAMs), and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) plays a crucial role in the extracellular matrix (ECM) remodeling and degradation activities. A wide range of substrates of the MP family includes ECM components, chemokines, cell receptors, and growth factors. Metalloproteinases activities are tightly regulated by proteolytic activation and inhibition via their natural inhibitors, tissue inhibitors of metalloproteinases (TIMPs), and the imbalance of the activation and inhibition is responsible in progression or inhibition of several diseases, e.g., cancer, neurological disorders, and cardiovascular diseases. We provide an overview of the structure, function, and the multifaceted role of MMPs, ADAMs, and TIMPs in several diseases via their cellular functions such as proteolysis of other cell signaling factors, degradation and remodeling of the ECM, and other essential protease-independent interactions in the ECM. The significance of MP inhibitors targeting specific MMP or ADAMs with high selectivity is also discussed. Recent advances and techniques used in developing novel MP inhibitors and MP responsive drug delivery tools are also reviewed.
17
Le, Q., S. Shah, H. Nguyen, S. Cortez, and W. Baricos. "A novel metalloproteinase present in freshly isolated rat glomeruli." American Journal of Physiology-Renal Physiology 260, no. 4 (April 1, 1991): F555—F561. http://dx.doi.org/10.1152/ajprenal.1991.260.4.f555.
Повний текст джерелаАнотація:
We have utilized [3H] gelatin to document high activity of a metalloproteinase present in freshly isolated rat glomeruli. [3H] gelatin degradation by glomeruli was markedly inhibited by EDTA (10 mM: -89 +/- 2.3%) and o-phenanthroline (2 mM: -72 +/- 0.1%), inhibitors of metalloproteinases. No significant inhibition of [3H]gelatin degradation was observed with inhibitors of serine or cysteine proteinases. Most (greater than 80%) of the glomerular metalloproteinase (GLOMP) activity was associated with the pellet after centrifugation of sonicated glomeruli at 100,000 g for 90 min. The pH optimum for gelatin degradation by sonicated glomeruli was approximately pH 8.5. Sodium dodecyl sulfate substrate (gelatin)-polyacrylamide gel electrophoresis revealed a single major band of EDTA-inhibitable gelatin-degrading activity with a molecular mass of approximately 116-125 kDa. The GLOMP activity was not inhibited by tissue inhibitors of metalloproteinases, did not appear to be latent, and was not activated by organomercurial activators of several latent metalloproteinases. GLOMP activity was increased 3.4-fold after incubation with trypsin (20 micrograms/ml, 25 min, 22 degrees C). These data indicate that GLOMP is distinct from the previously described matrix metalloproteinases, as well as other metalloproteinases present in the kidney, including the gelatinase secreted by cultured mesangial cells, Meprin, and endopeptidase 24.11 (enkephalinase, EC 3.4.24.11).
18
Martinho, Frederico C., Flávia F. C. Teixeira, Flávia G. R. Cardoso, Nádia S. Ferreira, Gustavo G. Nascimento, Cláudio A. T. Carvalho, and Márcia C. Valera. "Clinical Investigation of Matrix Metalloproteinases, Tissue Inhibitors of Matrix Metalloproteinases, and Matrix Metalloproteinase/Tissue Inhibitors of Matrix Metalloproteinase Complexes and Their Networks in Apical Periodontitis." Journal of Endodontics 42, no. 7 (July 2016): 1082–88. http://dx.doi.org/10.1016/j.joen.2016.04.001.
Повний текст джерела
19
Zhang, Yihe, Bingjie Jiang, Pengyuan Zhang, Sung K. Chiu, and Meng H. Lee. "Complete abrogation of key osteoclast markers with a membrane-anchored tissue inhibitor of metalloproteinase." Bone & Joint Research 11, no. 11 (November 1, 2022): 763–76. http://dx.doi.org/10.1302/2046-3758.1111.bjr-2022-0147.r2.
Повний текст джерелаАнотація:
Aims Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders. Methods We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP variant named ‘T1PrαTACE’ on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation. Results Osteoclast progenitor cells transduced with T1PrαTACE failed to form tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts or exhibit bone-resorbing activity following treatment with RANKL. At the messenger RNA level, T1PrαTACE strongly attenuated expression of key osteoclast marker genes that included TRAP, cathepsin K, osteoclast stimulatory transmembrane protein ( OC-STAMP), dendritic cell-specific transmembrane protein ( DC-STAMP), osteoclast-associated receptor ( OSCAR) , and ATPase H+-transporting V0 subunit d2 ( ATP6V0D2) by blocking autoamplification of nuclear factor of activated T cells 1 (NFATc1), the osteoclastogenic transcription factor. T1PrαTACE selectively extended p44/42 mitogen-activated protein kinase activation, an action that may have interrupted terminal differentiation of osteoclasts. Inhibition studies with broad-spectrum hydroxamate inhibitors confirmed that the anti-resorptive activity of T1PrαTACE was not reliant on its metalloproteinase-inhibitory activity. Conclusion T1PrαTACE disrupts the RANKL-NFATc1 signalling pathway, which leads to osteoclast dysfunction. As a novel candidate in the prevention of osteoclastogenesis, the TIMP could potentially be developed for the treatment of osteoclast-related disorders such as osteoporosis. Cite this article: Bone Joint Res 2022;11(11):763–776.
20
Stetler-Stevenson, W. G. "Tissue Inhibitors of Metalloproteinases in Cell Signaling: Metalloproteinase-Independent Biological Activities." Science Signaling 1, no. 27 (July 8, 2008): re6. http://dx.doi.org/10.1126/scisignal.127re6.
Повний текст джерела
21
Lee, Meng-Huee, Magdalini Rapti, and Gillian Murphy. "Total Conversion of Tissue Inhibitor of Metalloproteinase (TIMP) for Specific Metalloproteinase Targeting." Journal of Biological Chemistry 280, no. 16 (February 15, 2005): 15967–75. http://dx.doi.org/10.1074/jbc.m500897200.
Повний текст джерелаАнотація:
Tissueinhibitors ofmetalloproteinases (TIMPs) are the endogenous inhibitors of the matrix metalloproteinases, the ADAMs (adisintegrinandmetalloproteinase) and the ADAM-TS (ADAM withthrombospondin repeats) proteinases. There are four mammalian TIMPs (TIMP-1 to -4), and each TIMP has its own profile of metalloproteinase inhibition. TIMP-4 is the latest member of the TIMPs to be cloned, and it has never been reported to be active against the tumor necrosis factor-α-converting enzyme (TACE, ADAM-17). Here we examined the inhibitory properties of the full-length and the N-terminal domain form of TIMP-4 (N-TIMP-4) with TACE and showed that N-TIMP-4 is a far superior inhibitor than its full-length counterpart. Although full-length TIMP-4 displayed negligible activity against TACE, N-TIMP-4 is a slow tight-binding inhibitor with low nanomolar binding affinity. Our findings suggested that the C-terminal subdomains of the TIMPs have a significant impact over their activities with the ADAMs. To elucidate further the molecular basis that underpins TIMP/TACE interactions, we sculpted N-TIMP-4 with the surface residues of TIMP-3, the only native TIMP inhibitor of the enzyme. Transplantation of only three residues, Pro-Phe-Gly, onto the AB-loop of N-TIMP-4 resulted in a 10-fold enhancement in binding affinity; theKivalues of the resultant mutant were almost comparable with that of TIMP-3. Further mutation at the EF-loop supported our earlier findings on the preference of TACE for leucine at this locus. Drawing together our previous experience in TACE-targeted mutagenesis by using TIMP-1 and -2 scaffolds, we have finally resolved the mystery of the selective sensitivity of TACE to TIMP-3.
22
Yu, Anita E., Robert E. Hewitt, David E. Kleiner, and William G. Stetler-Stevenson. "Molecular regulation of cellular invasion— role of gelatinase A and TIMP-2." Biochemistry and Cell Biology 74, no. 6 (December 1, 1996): 823–31. http://dx.doi.org/10.1139/o96-088.
Повний текст джерелаАнотація:
Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much of the coordinate (physiological) or discoordinate (pathological) degradation of the ECM is catalyzed by a class of proteases known as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usually secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators and inhibitors. One member of the matrixin family, gelatinase A, is regulated differently from other MMPs, suggesting that it may play a unique role in cell–matrix interactions, including cell invasion. The conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a key event in the acquisition of invasive potential. This discussion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this process.Key words: tissue inhibitors of metalloproteinases, metalloproteinase, gelatinases, extracellular matrix, activation.
23
Bondar', I. A., and V. V. Klimontov. "The role of matrix metalloproteinases and their inhibitors in the development of renal fibrosis in the patients with diabetes mellitus." Problems of Endocrinology 58, no. 1 (February 15, 2012): 39–44. http://dx.doi.org/10.14341/probl201258139-44.
Повний текст джерелаАнотація:
The accumulation of components of extracellular matrix in the glomerular and interstitial compartments of the kidneys is a characteristic feature of diabetic nephropathy. The leading role in the extracellular matrix catabolism is played by matrix metalloproteinases (MMP). The activity of these enzymes is regulated by a group of inhibitors including tissue metalloproteinase inhibitors, plasminogen activator inhibitor-1, etc. Both in vivo and in vitro studies have demonstrated that a reduction of MMP activities and/or an increase of expression of MMP tissue inhibitors in the glomerular and tubular cells result in the suppression of catabolism of the components of extracellular matrix under the hyperglycemic conditions. Both circulating and urinary MMP as well as their inhibitors are considered to be new potential markers of renal fibrosis associated with diabetes mellitus. It is concluded that the directed activation of MMP and neutralization of their inhibitors provide a promising tool for the treatment of diabetic nephropathy.
24
Ye, Qi-Zhuang, Donald Hupe, and Linda Johnson. "Catalytic Domains of Matrix Metalloproteinases: A Molecular Biology Approach to Drug Discovery." Current Medicinal Chemistry 3, no. 6 (December 1999): 407–18. http://dx.doi.org/10.2174/0929867303999220307173246.
Повний текст джерелаАнотація:
Molecular biology has provided a range of tools for drug research. The work in the matrix metalloproteinase (MMP) catalytic domain area demonstrated one of the molecular biology approaches to drug discovery. Matrix metalloproteinases are a family of zinc containing proteinases involved in connective tissue remodeling and implicated in diseases such as arthritis, cancer metastasis, and periodontal diseases. Several catalytic domains of human MMPs have been expressed in E. coli and used for random inhibitor screening, protein/inhibitor complex structural determinations, and protein structure-function studies, promising a new generation of MMP inhibitors with high affinity, high selectivity, and high bioavailability as therapeutical agents.
25
Cawston, T. E., V. A. Curry, I. M. Clark, and B. L. Hazleman. "Identification of a new metalloproteinase inhibitor that forms tight-binding complexes with collagenase." Biochemical Journal 269, no. 1 (July 1, 1990): 183–87. http://dx.doi.org/10.1042/bj2690183.
Повний текст джерелаАнотація:
Connective-tissue cells produce a family of metalloproteinases which, once activated, can degrade all the components of the extracellular matrix. These potent enzymes are all inhibited by the tissue inhibitor of metalloproteinases (TIMP), and it was thought that the levels of this inhibitor controlled the extracellular activity of these enzymes. We recently detected a new metalloproteinase inhibitor present in culture media of WI-38 fibroblasts. The inhibitor, named ‘large inhibitor of metalloproteinases’ (LIMP), can be separated from TIMP by gel filtration on Ultrogel AcA 44, where it is eluted with an apparent Mr of 76,000. A portion of this inhibitor-containing peak binds to concanavalin A-Sepharose, indicating that at least some of the inhibitor contains carbohydrate. LIMP inhibits collagenase (MMP-1), stromelysin (MMP-3) and gelatinase (MMP-2) in a dose-dependent fashion. Collagenase forms tight-binding complexes with LIMP, which can be separated from free collagenase on gel-filtration columns. The complex is eluted with Mr 81,600 (AcA 44) or Mr 60,000 (Superose 12). This complex is larger than that formed between collagenase and TIMP, which has Mr 52,800 (Aca 44) or 41,000 (Superose 12). Polyclonal antibody to TIMP does not recognize LIMP by immunoblotting, and will not block the inhibition of collagenase by LIMP, showing that LIMP is not a multimeric form of TIMP. The role of this new inhibitor in connective-tissue breakdown studies and its relationship to previously described inhibitors of metalloproteinases is discussed.
26
Walker, P. D., G. P. Kaushal, and S. V. Shah. "Presence of a distinct extracellular matrix-degrading metalloproteinase activity in renal tubules." Journal of the American Society of Nephrology 5, no. 1 (July 1994): 55–61. http://dx.doi.org/10.1681/asn.v5155.
Повний текст джерелаАнотація:
Renal tubular homogenates incubated with [3H]laminin (2 micrograms, 10(5) cpm) at 37 degrees C resulted in time- and protein-dependent laminin degradation (e.g., at 24 h, control = 6,533 +/- 771; experimental = 27,610 +/- 1,023 cpm +/- SE; N = 20). Gel chromatography confirmed that laminin (800 to 900 kd) was degraded to 20- to 50-kd fragments. Laminin degradation was not significantly decreased by serine or cysteine protease inhibitors. In contrast, metal chelators produced marked inhibition (EDTA, 93 +/- 3%; 1,10-phenanthroline, 99 +/- 1%) indicating that, at neutral pH, metalloproteinases were responsible for the laminin degradation. Laminin-degrading activity in renal tubules was not inhibited by the tissue inhibitor of metalloproteinase and was present in an active form. This activity was also present in high concentrations in the renal cortex and medulla but was only minimal in the liver. Further studies of the renal cortex revealed a similar metalloproteinase activity against type IV collagen (11,075 +/- 305; N = 6) and gelatin (41,026 +/- 1,373; N = 6), and this activity was membrane associated (97 +/- 1%; N = 4). Taken together, the characteristics of this renal metalloproteinase indicate that it is distinct from classic matrix-degrading metalloproteinases. The release of this distinct metalloproteinase from damaged renal tubular epithelial cells during injury may result in the production of fragments of laminin or other extracellular matrix components with biologic effects relevant to renal regeneration.
27
Chernykh, V. V., V. I. Konenkov, O. V. Ermakova, N. B. Orlov, and A. N. Trunov. "Features of the level of matrix metalloproteinase-2, -3, -9 and tissue inhibitors of metalloproteinases-1, -2, -3, -4 in the aqueous humor of patients with primary open-angle glaucoma." Bulletin of Siberian Medicine 20, no. 4 (January 2, 2022): 86–92. http://dx.doi.org/10.20538/1682-0363-2021-4-86-92.
Повний текст джерелаАнотація:
Aim. To study the content of matrix metalloproteinase (MMP)-2, -3, -9 and tissue inhibitors of metalloproteinases (TIMPs) -1, -2, -3, -4 in the aqueous humor of patients with moderate primary open-angle glaucoma (POAG).Materials and methods. The experimental group included 47 patients with verified moderate primary open-angle glaucoma. The control group consisted of 26 patients with uncomplicated cataract. The levels of MMP-2, -3, -9 were determined with Luminex Performance Human MMP Magnetic Panel 3-plex kit (R&D Systems, USA), the concentration of TIMPs-1, -2, -3, - 4 was determined with the Human TIMP Magnetic Luminex Performance Assay 4-plex kit (R&D Systems, USA). The study was carried out using flow-through field fluorometry on a Bio-Plex 200 double-beam laser analyzer (Bio-Rad, USA).Results. The study showed a statistically significant increase in the levels of matrix metalloproteinase-2 and tissue inhibitors of matrix metalloproteinases-1, -2, -3, -4 in the aqueous humor of patients with moderate POAG compared with patients with uncomplicated cataract.Conclusion. The obtained data on high concentrations and imbalance in the levels of matrix metalloproteinases and their tissue inhibitors in the aqueous humor of patients with moderate POAG confirm the role of local inflammation, as well as impairments in the structure of the extracellular matrix and its remodeling in the mechanisms of development of this pathology.
28
Woessner Jr., J. Frederick. "Regulation of matrilysin in the rat uterus." Biochemistry and Cell Biology 74, no. 6 (December 1, 1996): 777–84. http://dx.doi.org/10.1139/o96-084.
Повний текст джерелаАнотація:
Matrilysin was first discovered in the involuting rat uterus; it has also been known as uterine metalloproteinase, putative metalloproteinase (Pump-1), and matrix metalloproteinase 7 (MMP-7). It is the smallest member (28 kDa) of a family of 15 MMPs that together are able to degrade most of the macromolecules of the extracellular matrix. This family is briefly reviewed; all members are zinc metalloproteinases that occur in zymogen form with the active site zinc blocked by cysteine. Matrilysin can degrade a wide range of gelatins, proteoglycans, and glycoproteins of the matrix and can activate several other MMPs including collagenase. With respect to the uterus, matrilysin is localized to epithelial cells and varies in amount with the estrus cycle and is found in high levels during postpartum involution. There is evidence for a role in the last stage of cervical ripening and immediately postpartum. Induction of premature delivery by onapristone and prostaglandin E2advances these changes in matrilysin. Regulation of the enzyme levels in the uterus are considered from four viewpoints: control of protein synthesis (particularly in response to hormones), activation of the proenzyme to functional protease, retention of enzyme by binding to matrix components such as heparan sulfate, and inhibition by natural inhibitors such as tissue inhibitor of metalloproteinases (TIMPs) and α2-macroglobulin.Key words: matrilysin, matrix metalloproteinases, TTMP, uterus, rat uterus.
29
Wang, Wei-Man, Gaoxiang Ge, N. H. Lim, Hideaki Nagase, and Daniel S. Greenspan. "TIMP-3 inhibits the procollagen N-proteinase ADAMTS-2." Biochemical Journal 398, no. 3 (August 29, 2006): 515–19. http://dx.doi.org/10.1042/bj20060630.
Повний текст джерелаАнотація:
ADAMTS-2 is an extracellular metalloproteinase responsible for cleaving the N-propeptides of procollagens I–III; an activity necessary for the formation of collagenous ECM (extracellular matrix). The four TIMPs (tissue inhibitors of metalloproteinases) regulate the activities of matrix metalloproteinases, which are involved in degrading ECM components. Here we delineate the abilities of the TIMPs to affect biosynthetic processing of procollagens. TIMP-1, -2 and -4 show no inhibitory activity towards ADAMTS-2, in addition none of the TIMPs showed inhibitory activity towards bone morphogenetic protein 1, which is responsible for cleaving procollagen C-propeptides. In contrast, TIMP-3 is demonstrated to inhibit ADAMTS-2 in vitro with apparent Ki values of 160 and 602 nM, in the presence of heparin or without respectively; and TIMP-3 is shown to inhibit procollagen processing by cells.
30
Morphy, J. R., T. A. Millican, and J. R. Porter. "Matrix Metalloproteinase Inhibitors: Current Status." Current Medicinal Chemistry 2, no. 3 (October 1995): 743–62. http://dx.doi.org/10.2174/092986730203220224091658.
Повний текст джерелаАнотація:
Abstract: Due to the increasing evidence for the involvement of the matrix metalloproteinases (MMPs) in a variety of tissue degenerative disorders, such as arthritis and cancer, there is considerable interest in designing agents which inhibit their action, either collectively or selectively. Historically, MMP inhibitors have been designed using knowledge of the substrate cleavage sites of the enzymes, early collagenase inhibitors bearing similarity to the cleavage site of type-1 collagen. This review will describe the recent design of specific inhibitors of stromelysin and gelatinase based upon their own substrate preferences. The structure of these inhibitors will be rationalised in terms of the recently published crystal structures of the MMPs. The development of a new generation of peptide-based, yet orally active, inhibitors will be reviewed and their progress towards the clinic assessed. Recent advances in the discovery of non-peptide MMP inhibitors will also be described.
31
Ågren, Magnus S., and Ulrich auf dem Keller. "Matrix Metalloproteinases: How Much Can They Do?" International Journal of Molecular Sciences 21, no. 8 (April 12, 2020): 2678. http://dx.doi.org/10.3390/ijms21082678.
Повний текст джерелаАнотація:
Zinc-dependent matrix metalloproteinases (MMPs) belong to metzincins that comprise not only 23 human MMPs but also other metalloproteinases, such as 21 human ADAMs (a disintegrin and metalloproteinase domain) and 19 secreted ADAMTSs (a disintegrin and metalloproteinase thrombospondin domain). The many setbacks from the clinical trials of broad-spectrum MMP inhibitors for cancer indications in the late 1990s emphasized the extreme complexity of the participation of these proteolytic enzymes in biology. This editorial mini-review summarizes the Special Issue, which includes four review articles and 10 original articles that highlight the versatile roles of MMPs, ADAMs, and ADAMTSs, in normal physiology as well as in neoplastic and destructive processes in tissue. In addition, we briefly discuss the unambiguous involvement of MMPs in wound healing.
32
Fukuda, Yuh, Masamichi Ishizaki, Yasunori Okada, Motoharu Seiki, and Nobuaki Yamanaka. "Matrix metalloproteinases and tissue inhibitor of metalloproteinase-2 in fetal rabbit lung." American Journal of Physiology-Lung Cellular and Molecular Physiology 279, no. 3 (September 1, 2000): L555—L561. http://dx.doi.org/10.1152/ajplung.2000.279.3.l555.
Повний текст джерелаАнотація:
Cell-extracellular matrix interaction and extracellular matrix remodeling are known to be important in fetal lung development. We investigated the localization of matrix metalloproteinases (MMPs) in fetal rabbit lungs. Immunohistochemistry for type IV collagen, MMP-1, MMP-2, MMP-9, membrane type (MT) 1 MMP, and tissue inhibitor of metalloproteinase (TIMP)-2 and in situ hybridization for MMP-9 mRNA were performed. Gelatin zymography and Western blotting for MT1-MMP in lung tissue homogenates were also studied. MMP-1 and MT1-MMP were detected in epithelial cells, and MMP-2 and TIMP-2 were detected in epithelial cells and some mesenchymal cells in each stage. MMP-9 was found in epithelial cells mainly in the late stage. Gelatin zymography revealed that the ratio of active MMP-2 to latent MMP-2 increased dramatically during the course of development. MT1-MMP was detected in tissue homogenates, especially predominant in the late stage. These findings suggest that MMPs and their inhibitors may contribute to the formation of airways and alveoli in fetal lung development and that activated MMP-2 of alveolar epithelial cells may function to provide an extremely wide alveolar surface.
33
Mun-Bryce, Sheila, and Gary A. Rosenberg. "Matrix Metalloproteinases in Cerebrovascular Disease." Journal of Cerebral Blood Flow & Metabolism 18, no. 11 (November 1998): 1163–72. http://dx.doi.org/10.1097/00004647-199811000-00001.
Повний текст джерелаАнотація:
Cerebral ischemia and intracerebral hemorrhage cause extensive damage to neurons, disrupt the extracellular matrix, and increase capillary permeability. Multiple substrates participate in the cellular damage, including free radicals and proteases. Matrix metalloproteinases and serine proteases are two classes of proteases that are normally present in brain in latent forms, but once activated, contribute to the injury process. These enzymes have a unique role in the remodeling of the extracellular matrix and in the modulation of the capillary permeability. Intracerebral injection of the matrix metalloproteinase, type IV collagenase, attacks the basal lamina around the capillary and opens the blood—brain barrier, Extracellular matrix-degrading proteases are induced by immediate early genes and cytokines, and regulated by growth factors. Activity of the matrix metalloproteinases is tightly controlled by activation mechanisms and tissue inhibitors of metalloproteinases. During ischemia and hemorrhage, multiple matrix metalloproteinases and serine proteases are produced along with their inhibitors. These proteolytic enzymes are involved in the delayed injury that accompanies the neuroinflammatory response. Synthetic inhibitors to metalloproteinases reduce proteolytic tissue damage, and may limit secondary neuroinflammation.
34
Jung, Klaus, Michael Lein, Norbert Ulbrich, Birgit Rudolph, Wolfgang Henke, Dietmar Schnorr, and Stefan A. Loening. "Quantification of matrix metalloproteinases and tissue inhibitors of metalloproteinase in prostatic tissue: Analytical aspects." Prostate 34, no. 2 (February 1, 1998): 130–36. http://dx.doi.org/10.1002/(sici)1097-0045(19980201)34:2<130::aid-pros8>3.0.co;2-o.
Повний текст джерела
35
Usenko, Yu, and Ya Yu Voitiv. "Genetic and morphological aspects of the enterocutaneous fistula development." Klinicheskaia khirurgiia 87, no. 7-8 (September 30, 2020): 38–42. http://dx.doi.org/10.26779/2522-1396.2020.7-8.38.
Повний текст джерелаАнотація:
Objective. To analyze the frequency of polymorphic variants of matrix metalloproteinase-2 (C-1306 → T) and tissue inhibitors of metalloproteinase-2 (G303 → A) genes in patients with enterocutaneous fistulas and to identify the connection with morphological changes of connective tissue.
Materials and methods. The object of the study comprises 24 patients with enterocutaneous fistula who were treated in the Shalimov National Institute of Surgery and Transplantology during 2016-2020. Laboratory, genetic, histological studies and statistical analysis were performed.
Results. As a result of genetic and statistical analysis of the matrix metalloproteinase-2 (C-1306→T) and tissue inhibitors of metalloproteinase-2 (G303→A) gene single nucleotide polymorphisms, genotype variants have been identified that are associated with the risk of enterocutaneous fistula development. Immunohistochemical examination of tissues with monoclonal antibodies to α-smooth muscle actin (α-SMA) revealed uneven, focal expression in smooth muscle differentiation cells and fibroblasts. Examination with monoclonal antibodies to Collagen IV there is a moderate positive expression in the basement membrane of blood vessels, in smooth muscle cells of the muscular layer of the vascular wall, in areas of connective tissue.
Conclusion. Enterocutaneous fistula is 1,5 times more common in carriers of homozygous GG genotype of the tissue inhibitors of metalloproteinase-2 (G303→A) gene and twice less common in heterozygotes GA (25% vs. 40%, p=0,057). Carriers of minor homozygotes of AA genotype in the group with enterocutaneous fistula were not detected, while a similar genotype in the control group was found in 10% of cases. Immunohistochemical examination of small and large intestine tissues with monoclonal antibodies to Collagen IV and α-SMA revealed signs of pathological connective tissue remodeling.
36
Liva, Francesca, Doretta Cuffaro, Elisa Nuti, Susanna Nencetti, Elisabetta Orlandini, Giovanni Vozzi, and Armando Rossello. "Age-related Macular Degeneration: Current Knowledge of Zinc Metalloproteinases Involvement." Current Drug Targets 20, no. 9 (June 11, 2019): 903–18. http://dx.doi.org/10.2174/1389450120666190122114857.
Повний текст джерелаАнотація:
Background: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. The disease is characterized by photoreceptor loss in the macula and reduced Retinal Pigment Epithelium (RPE) function, associated with matrix degradation, cell proliferation, neovascularization and inflammation. Matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play a critical role in the physiology of extracellular matrix (ECM) turnover and, in turn, in ECM pathologies, such as AMD. A balance between the activities of MMPs and Tissue Inhibitors of Metalloproteinase (TIMPs) is crucial for the integrity of the ECM components; indeed, a dysregulation in the ratio of these factors produces profound changes in the ECM, including thickening and deposit formation, which eventually might lead to AMD development. Objective: This article reviews the relevance and impact of zinc metalloproteinases on the development of AMD and their roles as biomarkers and/or therapeutic targets. We illustrate some studies on several inhibitors of MMPs currently used to dissect physiological properties of MMPs. Moreover, all molecules or technologies used to control MMP and ADAM activity in AMD are analyzed. Conclusion: This study underlines the changes in the activity of MMPs expressed by RPE cells, highlights the functions of already used MMP inhibitors and consequently suggests their application as therapeutic agents for the treatment of AMD.
37
Koon, Hon-Wai, Dezheng Zhao, Xi Na, Mary P. Moyer та Charalabos Pothoulakis. "Metalloproteinases and Transforming Growth Factor-α Mediate Substance P-induced Mitogen-activated Protein Kinase Activation and Proliferation in Human Colonocytes". Journal of Biological Chemistry 279, № 44 (19 серпня 2004): 45519–27. http://dx.doi.org/10.1074/jbc.m408523200.
Повний текст джерелаАнотація:
Substance P (SP) participates in acute intestinal inflammation via binding to the G-protein-coupled neurokinin-1 receptor (NK-1R) and release of proinflammatory cytokines from colonic epithelial cells. SP also stimulates cell proliferation, a critical event in tissue healing during chronic colitis, via transactivation of the epidermal growth factor (EGF) receptor (EGFR) and activation of mitogen-activated protein kinase (MAPK). Here we examined the mechanism by which SP induces EGFR and MAPK activation. We used non-transformed human NCM460 colonocytes stably transfected with the human NK-1R (NCM460-NK-1R cells) as well as untransfected U373 MG cells expressing high levels of endogenous NK-1R. Exposure of both cell lines to SP (10–7m) stimulated EGFR activation (1 min) followed by extracellular signal-regulated protein kinase (ERK1/2) activation (2–5 min). SP-induced ERK1/2 activation was blocked by pretreatment with the metalloproteinase inhibitor Batimastat/GM6001, the EGFR phosphorylation inhibitor AG1478, and the tumor necrosis factor-α-converting enzyme (TACE) inhibitor TAPI-1. Pretreatment with antibodies against potential EGFR ligands suggested that transforming growth factor-α (TGFα), but not the other EGFR ligands EGF, heparin-binding EGF, or amphiregulin, mediates SP-induced EGFR transactivation. SP stimulated TGFα release into the extracellular space that was measurable within 2 min, and this release was inhibited by metalloproteinase inhibitors and the TACE inhibitor TAPI-1. SP also induced MAPK-mediated cell proliferation that was inhibited by TACE, matrix metalloproteinase (MMP), EGFR, and MEK1 inhibitors. Thus, in human colonocytes, NK-1R-induced EGFR and MAPK activation and cell proliferation involve matrix metalloproteinases (most likely TACE) and the release of TGFα. These signaling mechanisms may be involved in the protective effects of NK-1R in chronic colitis.
38
Seizer, Peter, and Andreas E. May. "Platelets and matrix metalloproteinases." Thrombosis and Haemostasis 110, no. 11 (2013): 903–9. http://dx.doi.org/10.1160/th13-02-0113.
Повний текст джерелаАнотація:
SummaryMatrix metalloproteinases (MMPs) and their inhibitors essentially contribute to a variety of pathophysiologies by modulating cell migration, tissue degradation and inflammation. Platelet-associated MMP activity appears to play a major role in these processes. First, platelets can concentrate leukocyte-derived MMP activity to sites of vascular injury by leukocyte recruitment. Second, platelets stimulate MMP production in e.g. leukocytes, endothelial cells, or tumour cells by direct receptor interaction or/and by paracrine pathways. Third, platelets synthesise and secrete a variety of MMPs including MMP-1, MMP-2, MMP-3, and MMP-14 (MT1-MMP), and potentially MMP-9 as well as the tissue inhibitors of metalloproteinase (TIMPs). This review focuses on platelet-derived and platelet-induced MMPs and their inhibitors.
39
Ichiyama, Takashi, Tsuneo Morishima, Madoka Kajimoto, Takeshi Matsushige, Tomoyo Matsubara, and Susumu Furukawa. "MATRIX METALLOPROTEINASE-9 AND TISSUE INHIBITORS OF METALLOPROTEINASES 1 IN INFLUENZA-ASSOCIATED ENCEPHALOPATHY." Pediatric Infectious Disease Journal 26, no. 6 (June 2007): 542–44. http://dx.doi.org/10.1097/inf.0b013e31803994a0.
Повний текст джерела
40
Li, Y. "Proinflammatory cytokines regulate tissue inhibitors of metalloproteinases and disintegrin metalloproteinase in cardiac cells." Cardiovascular Research 42, no. 1 (April 1, 1999): 162–72. http://dx.doi.org/10.1016/s0008-6363(98)00297-1.
Повний текст джерела
41
Strup-Perrot, Carine, Denis Mathé, Christine Linard, Dominique Violot, Fabien Milliat, Agnès François, Jean Bourhis, and Marie-Catherine Vozenin-Brotons. "Global gene expression profiles reveal an increase in mRNA levels of collagens, MMPs, and TIMPs in late radiation enteritis." American Journal of Physiology-Gastrointestinal and Liver Physiology 287, no. 4 (October 2004): G875—G885. http://dx.doi.org/10.1152/ajpgi.00088.2004.
Повний текст джерелаАнотація:
Radiation enteritis, a common complication of radiation therapy for abdominal and pelvic cancers, is characterized by severe transmural fibrosis associated with mesenchymal cell activation, tissue disorganization, and deposition of fibrillar collagen. To investigate the mechanisms involved in this pathological accumulation of extracellular matrix, we studied gene expression of matrix components along with that of genes involved in matrix remodeling, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs). Hybrid selection on high-density cDNA array, real-time RT-PCR, gelatin zymography and imunohistochemistry were used to characterize the mRNA expression profile, activity, and tissue location of extracellular matrix-related genes in radiation enteritis compared with healthy ileum. cDNA array analysis revealed a strong induction of genes coding for collagens I, III, IV, VI, and VIII, SPARC, and tenascin-C, extracellular-matrix degrading enzymes (MMP-1, -2, -3, -14, -18+19), and metalloproteinase inhibitors (TIMP-1, -2, plasminogen activator inhibitor-1) in radiation enteritis. This increase was correlated with the degree of infiltration of the mucosa by inflammatory cells, and the presence of differentiated mesenchymal cells in the submucosa and muscularis propria. Despite the fact that expression of collagens, MMPs, and TIMPs simultaneously increase, quantification of net collagen deposition shows an overall accumulation of collagen. Our results indicate that late radiation enteritis tissues are subjected to active process of fibrogenesis as well as fibrolysis, with a balance toward fibrogenesis. This demonstrates that established fibrotic tissue is not scarred fixed tissue but is subjected to a dynamic remodeling process.
42
Lim, Ngee H., Masahide Kashiwagi, Robert Visse, Jonathan Jones, Jan J. Enghild, Keith Brew, and Hideaki Nagase. "Reactive-site mutants of N-TIMP-3 that selectively inhibit ADAMTS-4 and ADAMTS-5: biological and structural implications." Biochemical Journal 431, no. 1 (September 14, 2010): 113–22. http://dx.doi.org/10.1042/bj20100725.
Повний текст джерелаАнотація:
We have reported previously that reactive-site mutants of N-TIMP-3 [N-terminal inhibitory domain of TIMP-3 (tissue inhibitor of metalloproteinases 3)] modified at the N-terminus, selectively inhibited ADAM17 (a disintegrin and metalloproteinase 17) over the MMPs (matrix metalloproteinases). The primary aggrecanases ADAMTS (ADAM with thrombospondin motifs) -4 and -5 are ADAM17-related metalloproteinases which are similarly inhibited by TIMP-3, but are poorly inhibited by other TIMPs. Using a newly developed recombinant protein substrate based on the IGD (interglobular domain) of aggrecan, gst-IGD-flag, these reactive-site mutants were found to similarly inhibit ADAMTS-4 and ADAMTS-5. Further mutations of N-TIMP-3 indicated that up to two extra alanine residues can be attached to the N-terminus before the Ki (app) for ADAMTS-4 and ADAMTS-5 increased to over 100 nM. No other residues tested at the [−1] position produced inhibitors as potent as the alanine mutant. The mutants N-TIMP-3(T2G), [−1A]N-TIMP-3 and [−2A]N-TIMP-3 were effective inhibitors of aggrecan degradation, but not of collagen degradation in both IL-1α (interleukin-1α)-stimulated porcine articular cartilage explants and IL-1α with oncostatin M-stimulated human cartilage explants. Molecular modelling studies indicated that the [−1A]N-TIMP-3 mutant has additional stabilizing interactions with the catalytic domains of ADAM17, ADAMTS-4 and ADAMTS-5 that are absent from complexes with MMPs. These observations suggest that further mutation of the residues of N-TIMP-3 which make unique contacts with these metalloproteinases may allow discrimination between them.
43
Saunders, W. Brian, Brenda L. Bohnsack, Jennifer B. Faske, Nicholas J. Anthis, Kayla J. Bayless, Karen K. Hirschi, and George E. Davis. "Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3." Journal of Cell Biology 175, no. 1 (October 9, 2006): 179–91. http://dx.doi.org/10.1083/jcb.200603176.
Повний текст джерелаАнотація:
The endothelial cell (EC)–derived tissue inhibitor of metalloproteinase-2 (TIMP-2) and pericyte-derived TIMP-3 are shown to coregulate human capillary tube stabilization following EC–pericyte interactions through a combined ability to block EC tube morphogenesis and regression in three-dimensional collagen matrices. EC–pericyte interactions strongly induce TIMP-3 expression by pericytes, whereas ECs produce TIMP-2 in EC–pericyte cocultures. Using small interfering RNA technology, the suppression of EC TIMP-2 and pericyte TIMP-3 expression leads to capillary tube regression in these cocultures in a matrix metalloproteinase-1 (MMP-1)–, MMP-10–, and ADAM-15 (a disintegrin and metalloproteinase-15)–dependent manner. Furthermore, we show that EC tube morphogenesis (lumen formation and invasion) is primarily controlled by the TIMP-2 and -3 target membrane type (MT) 1 MMP. Additional targets of these inhibitors include MT2-MMP and ADAM-15, which also regulate EC invasion. Mutagenesis experiments reveal that TIMP-3 requires its proteinase inhibitory function to induce tube stabilization. Overall, these data reveal a novel role for both TIMP-2 and -3 in the pericyte-induced stabilization of newly formed vascular networks that are predisposed to undergo regression and reveal specific molecular targets of the inhibitors regulating these events.
44
Rapti, Magdalini, Susan J. Atkinson, Meng-Huee Lee, Andrew Trim, Marcia Moss, and Gillian Murphy. "The isolated N-terminal domains of TIMP-1 and TIMP-3 are insufficient for ADAM10 inhibition." Biochemical Journal 411, no. 2 (March 27, 2008): 433–39. http://dx.doi.org/10.1042/bj20071430.
Повний текст джерелаАнотація:
ADAM (a disintegrin and metalloproteinase) 10 is a key member of the ADAM family of disintegrin and metalloproteinases which process membrane-associated proteins to soluble forms in a process known as ‘shedding’. Among the major targets of ADAM10 are Notch, EphrinA2 and CD44. In many cell-based studies of shedding, the activity of ADAM10 appears to overlap with that of ADAM17, which has a similar active-site topology relative to the other proteolytically active ADAMs. The tissue inhibitors of metalloproteinases, TIMPs, have proved useful in the study of ADAM function, since TIMP-1 inhibits ADAM10, but not ADAM17; however, both enzymes are inhibited by TIMP-3. In the present study, we show that, in comparison with ADAM17 and the MMPs (matrix metalloproteinases), the N-terminal domains of TIMPs alone are insufficient for the inhibition of ADAM10. This knowledge could form the basis for the design of directed inhibitors against different metalloproteinases.
45
Nasution, Aini Hariyani, Lidya Irani Nainggolan, and Widianto Meydhyono. "Comparison of matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 levels and alveolar bone density in chronic periodontitis before and after scaling and root planning." Majalah Kedokteran Gigi Indonesia 8, no. 2 (November 24, 2022): 98. http://dx.doi.org/10.22146/majkedgiind.66221.
Повний текст джерелаАнотація:
Periodontitis is typically associated with disorders characterized by compromised tooth-supporting tissue. Damage to periodontal tissue is caused by an imbalance between matrix metalloproteinases and their inhibitors. Decreased tissue inhibitor and elevated matrix metalloproteinase levels result in collagen connective tissue and bone degradation. Several studies have shown that high levels of matrix metalloproteinase-13 (MMP-13) and low levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) are also found in gingival crevicular fluid and saliva of patients with periodontitis. The purpose of this study was to determine the comparison of MMP-13 levels, TIMP-1 levels of saliva and bone density in patients with chronic periodontitis before and after scaling and root planning (SRP). The study samples were selected from patients who came for treatment at the Periodontics Installation of Universitas Sumatera Utara. A total of 16 patients were selected (n = 16) with a diagnosis of chronic periodontitis. The result showed that salivary MMP-13 levels in chronic periodontitis patients before SRP were higher than salivary MMP-13 levels after SRP and the difference was statistically significant (p < 0.05). It was also revealed that salivary TIMP-1 levels and alveolar bone density in chronic periodontitis patients before SRP were lower than that after SRP and the difference was statisticallysignificant (p < 0.05). There was a positive correlation between clinical parameters and salivary MMP-13 levels in patients with chronic periodontitis before and after SRP, but it was not statistically significant (p > 0.05). There was a negative correlation between clinical parameters and salivary TIMP-1 levels in patients with chronic periodontitis before and after SRP, but it was not statistically significant (p > 0.05).
46
NAGASE, Hideaki, Ko SUZUKI, Tim E. CAWSTON, and K. BREW. "Involvement of a region near valine-69 of tissue inhibitor of metalloproteinases (TIMP)-1 in the interaction with matrix metalloproteinase 3 (stromelysin 1)." Biochemical Journal 325, no. 1 (July 1, 1997): 163–67. http://dx.doi.org/10.1042/bj3250163.
Повний текст джерелаАнотація:
Tissue inhibitors of metalloproteinases (TIMPs) inhibit matrix metalloproteinases (MMPs) by forming a 1:1 stoichiometric complex, but the inhibition mechanism of these inhibitors is not known. Here we have investigated the reactive site of TIMP-1 by its proteinase susceptibility before and after forming a complex with MMP-3 (stromelysin 1). When TIMP-1 was allowed to react with human neutrophil elastase, its inhibitory activity was destroyed. This resulted from cleavage of the Val69–Cys70 bond. However, cleavage of this bond by neutrophil elastase was prevented when TIMP-1 formed a complex with the catalytic domain of MMP-3, and full TIMP-1 activity was restored after dissociation of the complex at pH 3.0 in the presence of EDTA. These results indicate that the region around Val69 closely associates with an active MMP. The three-dimensional structure of the N-terminal domain of TIMP-2 elucidated by NMR studies [Williamson, Martorell, Carr, Murphy, Docherty, Freedman and Feeney (1994) Biochemistry 33, 11745–11759] reveals that Val69 and Cys70 form part of an extended ridge that also includes the N-terminal section of the inhibitor. This region is probably involved in the interaction with the catalytic domains of MMPs.
47
Khunluck, Tueanjai, Veerapol Kukongviriyapan, Laddawan Senggunprai, Wutthipong Duangarsong, and Auemduan Prawan. "The Inhibition Kinetics and Potential Anti-Migration Activity of NQO1 Inhibitory Coumarins on Cholangiocarcinoma Cells." Integrative Cancer Therapies 18 (December 25, 2018): 153473541882044. http://dx.doi.org/10.1177/1534735418820444.
Повний текст джерелаАнотація:
Altered expression of a cytosolic flavoenzyme NAD(P)H:quinone oxidoreductase-1 (NQO1) has been seen in many human tumors. Its remarkable overexpression in cholangiocarcinoma (CCA; an aggressive malignancy of the biliary duct system) was associated with poor prognosis and short survival of the patients. Inhibition of NQO1 has been proposed as a potential strategy to improve the efficacy of anticancer drugs in various cancers including CCA. This study investigated novel NQO1 inhibitors and verified the mechanisms of their enzyme inhibition. Among the different chemical classes of natural NQO1 inhibitors are coumarins, flavonoids, and triterpenoids. Coumarins are a group of particularly potent NQO1 inhibitors. The mechanisms and kinetics of enzyme inhibition of coumarin, aesculetin, umbelliferone, and scopoletin using the cell lysates as a source of NQO1 enzyme best fit with an uncompetitive inhibition model. Among the NOQ1 inhibitors tested in KKU-100 CCA cells, scopoletin and umbelliferone had the strongest inhibitory effect on this enzyme, while aesculetin and coumarin barely affected intracellular NQO1. All coumarins were further tested for cytotoxicity and anti-migration activity. At modest cytotoxic doses, scopoletin and umbelliferone greatly inhibited the migration of KKU-100 cells, whereas coumarin and aesculetin barely reduced cell migration. The anti-migration effect of scopoletin was associated with decreased ratio of matrix metalloproteinase 9/tissue inhibitors of metalloproteinases 1 ( MMP9/ TIMP1) mRNA. These findings suggest that natural compounds with potent inhibitory effect on intracellular NQO1 have useful anti-migration effects on CCA cells. In order to prove that the potent NQO1 inhibitor, scopoletin, is clinically useful in the enhancement of CCA treatment, additional in vivo studies to elucidate the mechanism of these effects are needed.
48
Liu, Xu-Wen, Marcus E. Taube, Ki-Kyung Jung, Zhong Dong, Yong J. Lee, Stefanie Roshy, Bonnie F. Sloane, Rafael Fridman, and Hyeong-Reh Choi Kim. "Tissue Inhibitor of Metalloproteinase-1 Protects Human Breast Epithelial Cells from Extrinsic Cell Death: A Potential Oncogenic Activity of Tissue Inhibitor of Metalloproteinase-1." Cancer Research 65, no. 3 (February 1, 2005): 898–906. http://dx.doi.org/10.1158/0008-5472.898.65.3.
Повний текст джерелаАнотація:
Abstract Tissue inhibitors of metalloproteinases (TIMPs) inhibit matrix metalloproteinases and some members of a disintegrin and metalloproteinase domain (ADAM) family. In addition, recent studies unveiled novel functions of TIMPs in the regulation of apoptosis. TIMP-1 inhibits intrinsic apoptosis by inducing TIMP-1 specific cell survival pathways involving focal adhesion kinase (FAK). TIMP-3, however, was shown to enhance extrinsic cell death by inhibiting the shedding of the cell surface death receptors mediated by tumor necrosis factor-α converting enzymes (TACE/ADAM-17). Here, we examined whether TIMP-1, an inhibitor of some of the ADAM family members, enhances the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)–induced extrinsic apoptotic pathway. Surprisingly, we found that TIMP-1 effectively protects human breast epithelial cells from TRAIL-induced apoptosis, demonstrating opposite roles of TIMP-1 and TIMP-3 for the regulation of extrinsic apoptosis. TIMP-1 inhibition of TRAIL-induced apoptosis does not depend on its ability to inhibit matrix metalloproteinases or ADAM activities and is unrelated to its ability to stabilize active or decoy death receptors. Importantly, inhibition of PI 3-kinase signaling by wortmannin and down-regulation of FAK expression using siRNA significantly diminish TIMP-1 protection of human breast epithelial cells against TRAIL-induced extrinsic apoptosis. In addition, the in vitro three-dimensional culture studies showed that TIMP-1 inhibits lumen formation and apoptosis during morphogenesis of MCF10A acini. Taken together, these studies suggest that TIMP-1 may exert oncogenic activity in breast cancer through inhibition of both intrinsic and extrinsic apoptosis involving the FAK survival signal transduction pathway.
49
Wang, Ling-Li, Bing Zhang, Ming-Hua Zheng, Yu-Zhong Xie, Chang-Jiang Wang, and Jing-Yi Jin. "Matrix Metalloproteinases (MMPs) in Targeted Drug Delivery: Synthesis of a Potent and Highly Selective Inhibitor against Matrix Metalloproteinase- 7." Current Topics in Medicinal Chemistry 20, no. 27 (November 10, 2020): 2459–71. http://dx.doi.org/10.2174/1568026620666200722104928.
Повний текст джерелаАнотація:
Background: Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases that play a key role in both physiological and pathological tissue degradation. MMPs have reportedly shown great potentials in the degradation of the Extracellular Matrix (ECM), have shown great potentials in targeting bioactive and imaging agents in cancer treatment. MMPs could provoke Epithelial to Mesenchymal Transition (EMT) of cancer cells and manipulate their signaling, adhesion, migration and invasion to promote cancer cell aggressiveness. Therefore, targeting and particularly inhibiting MMPs within the tumor microenvironment is an effective strategy for cancer treatment. Based on this idea, different MMP inhibitors (MMPIs) have been developed to manipulate the tumor microenvironment towards conditions appropriate for the actions of antitumor agents. Studies are ongoing to improve the selectivity and specificity of MMPIs. Structural optimization has facilitated the discovery of selective inhibitors of the MMPs. However, so far no selective inhibitor for MMP-7 has been proposed. Aims: This study aims to comprehensively review the potentials and advances in applications of MMPs particularly MMP-7 in targeted cancer treatment approaches with the main focus on targeted drug delivery. Different targeting strategies for manipulating and inhibiting MMPs for the treatment of cancer are discussed. MMPs are upregulated at all stages of expression in cancers. Different MMP subtypes have shown significant targeting applicability at the genetic, protein, and activity levels in both physiological and pathophysiological conditions in a variety of cancers. The expression of MMPs significantly increases at advanced cancer stages, which can be used for controlled release in cancers in advance stages. Methods: Moreover, this study presents the synthesis and characteristics of a new and highly selective inhibitor against MMP-7 and discusses its applications in targeted drug delivery systems for therapeutics and diagnostics modalities. Results: Our findings showed that the structure of the inhibitor P3’ side chains play the crucial role in developing an optimized MMP-7 inhibitor with high selectivity and significant degradation activities against ECM. Conclusion: Optimized NDC can serve as a highly potent and selective inhibitor against MMP-7 following screening and optimization of the P3’ side chains, with a Ki of 38.6 nM and an inhibitory selectivity of 575 of MMP-7 over MMP-1.
50
Curran, Stephanie, Sinclair R. Dundas, Jenny Buxton, Matthew F. Leeman, Robin Ramsay, and Graeme I. Murray. "Matrix Metalloproteinase/Tissue Inhibitors of Matrix Metalloproteinase Phenotype Identifies Poor Prognosis Colorectal Cancers." Clinical Cancer Research 10, no. 24 (December 15, 2004): 8229–34. http://dx.doi.org/10.1158/1078-0432.ccr-04-0424.
Повний текст джерела