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Chia, Choy May. "Epidermal growth factor (EGF) : transforming growth factor alpha (TGF-#alpha#) in human preimplantation development." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362631.
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Lau, Kwok-pui. "Clinicopathological roles of transforming growth factor alpha (TGF[alpha]) in papillary thyroid carcinoma /." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/HKUTO/record/B39558733.
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Lam, Sze-man Joyce. "Expression of transforming growth factors (TGF-alpha and TGF-beta 1) on postmortem skin wounds /." View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38480566.
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Liu, Xiaoying. "Molecular mechanisms of myofibroblast differentiation and the role of TGF beta1, TNF alpha, and thrombin signal transduction." Columbus, Ohio : Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1236711907.
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Glinsmann-Gibson, Betty Jean 1961. "Molecular mechanism of autocrine regulation by TGF-alpha in T(3)M(4) human pancreatic carcinoma cells." Thesis, The University of Arizona, 1989. http://hdl.handle.net/10150/277113.
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The human pancreatic cancer cell line T3M4, is known to produce transforming growth factor-alpha (TGF-alpha); as well as overexpress the receptor for this ligand, epidermal growth factor (EGF) receptor. TGF-alpha messenger RNA (mRNA) levels were assayed using northern blot, after addition of epidermal growth factor or TGF-alpha. The level of TGF-alpha mRNA was found to increase 2-fold at 2 hours and then return to near basal levels at 10 hours, after treatment with either ligand. Both ligands were also equipotent in a 2 hour dose response assay, with half maximal stimulation seen at 1 nM and maximal stimulation reached at 4 nM. Furthermore, there appeared to be a 2-fold increase in TGF-alpha transcription as determined by nuclear runoff experiments. Induction of TGF-alpha mRNA coupled with the overexpression of the EGF receptor, may result in a potent autocrine cycle; which may be found in other cancers.
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Hallbeck, Anna-Lotta. "Studies of transforming growth factor alpha in normal and abnormal growth." Doctoral thesis, Linköping : Univ, 2007. http://www.bibl.liu.se/liupubl/disp/disp2007/med1025s.pdf.
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林詩敏 and Sze-man Joyce Lam. "Expression of transforming growth factors (TGF-alpha and TGF-beta 1) on postmortem skin wounds." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B45011400.
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Kiesow, Claudia. "Pathogenese der equinen Endometrose: Bedeutung der Wachstumsfaktoren Transforming growth factor-alpha, -beta1, -beta2 und -beta3 sowie der Matrixmetalloproteinase-2." Doctoral thesis, Universitätsbibliothek Leipzig, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-65079.
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Ziel der vorliegenden Arbeit war die immunhistologische Charakterisierung der Expression der profibrotischen Wachstumsfaktoren Transforming growth factor-beta-1, -beta2 und -beta3 und des Enzyms Matrixmetalloproteinase-2 (MMP-2) im equinen Endometrium während des Zyklus sowie innerhalb der verschiedenen Erscheinungsformen der equinen Endometrose. Zudem wurde der potentielle Einfluss einer gleichzeitig auftretenden Endometritis auf die glanduläre und stromale Wachstumsfaktor- und Enzym-Expression untersucht. Die Ergebnisse dieser Studie sollten klären, ob und inwieweit den untersuchten Wachstumsfaktoren unter Beteiligung von MMP-2 in der Pathogenese der equinen Endometrose eine mit anderen Organfibrosen vergleichbare Schlüsselrolle zukommt.
Zu diesem Zweck standen an definierten Tagen entnommene Endometriumbioptate (n=21) von drei zyklisch aktiven, klinisch und gynäkologisch gesunden Maidenstuten sowie Endometriumbioptate von 60 Stuten mit graduell variabler Endometrose unterschiedlichen Charakters und Endometriumbioptate von 22 Stuten mit mittelgradiger Endometrose und gleichzeitiger mittelgradiger eitriger (n=16) bzw. nichteitriger (n=6) Endometritis aus dem Routineeinsendungsmaterial des Institutes für Veterinär-Pathologie der Universität Leipzig zur Verfügung.
Die Wachstumsfaktoren TGF-beta1, -beta2 und -beta3 sowie das Enzym MMP-2 zeigen im Zyklus ein typisches, zellspezifisches Reaktionsmuster, das unterschiedlichen Regulations-mechanismen zu unterliegen scheint. Ein Maximum der TGF-beta1-Expression in den luminalen Epithelzellen, Stroma- und Drüsenzellen kann in der endometrialen Sekretionsphase mit Anstieg bzw. einem Maximum der Serumprogesteron-Konzentration beobachtet werden. Im Gegensatz dazu tritt eine Expression von MMP-2 in den Stromazellen in der Sekretionsphase mit Abfall der Progesteronkonzentration im Serum auf. Das luminale Epithel und die Stromazellen zeigen eine maximale Expression von TGF-beta2 beim Vorliegen hoher Progesteronspiegel im Serum bzw. mit Abfall der Serumprogesteron-Konzentration in der Sekretionsphase. TGF-beta3 weist im luminalen Epithel ein ähnliches Expressionsmuster auf, eine deutliche Abhängigkeit zu den Serumhormon-Konzentrationen lässt sich jedoch nicht feststellen. Die stromale Expression von TGF-alpha unterliegt im equinen Endometrium keinen zyklusabhängigen Variationen.
Die Stromazellen innerhalb der verschiedenen Endometroseherde zeigen, im Vergleich zum unveränderten Endometrium, vor allem eine verminderte Expression von TGF-alpha. Das Expressionsmuster der TGF-beta-Wachstumsfaktoren ist grundsätzlich variabel, es fällt jedoch auf, dass die Stromazellen insbesondere in inaktiven Endometrosen eine geringere Expression der TGF-beta-Isoformen aufweisen. Ursache ist möglicherweise eine gestörte hormonelle Stimulation bzw. eine stromale Synthesestörung in Folge veränderter epithelial/stromaler Wechselwirkungen. Das Enzym MMP-2 wird dagegen in den Stromazellen aller Endometroseherde, unabhängig von deren Differenzierung und dem Auftreten glandulärer Alterationen, deutlich vermehrt nachgewiesen. Dies ist sehr wahrscheinlich Folge der Extra-zellularmatrix-Akkumulation innerhalb der Endometroseherde und für die fortschreitende Zerstörung der glandulären Basalmembranen verantwortlich. Die glanduläre Expression innerhalb der Endometroseherde gleicht weitgehend der der unveränderten Drüsenzellen, lediglich in destruierenden Endometrosen werden TGF-alpha, TGF-beta2 und MMP-2 in den involvierten Drüsenzellen vermehrt nachgewiesen. Mögliche Ursachen wären eine Diffusion durch die geschädigte glanduläre Basalmembran bzw. eine Anregung der Synthese im Rahmen der epithelialen Wundheilung. Eine Anregung der glandulären und stromalen Expression der untersuchten Wachstumsfaktoren und des Enzyms MMP-2 im Rahmen der Endometrose durch die Anwesenheit von Entzündungszellen konnte nicht nachgewiesen werden.
Eine der Leber- und Lungenfibrose ähnelnde, überschießende Wundheilungsreaktion durch eine primär epithelial bedingte, vermehrte TGF-Wachstumsfaktorproduktion sowie direkte Zusammenhänge zwischen der MMP-2- und TGF-beta-Wachstumsfaktor-Expression waren in der equinen Endometrose nicht festzustellen. Da vor allem die Stromazellen in der Endometrose eine veränderte Expression der Wachstumsfaktoren aufwiesen, ist möglicherweise eine primäre stromale Fehldifferenzierung der Ausgangspunkt für die Entstehung der Endometrose. Eine mit der Leber- und Lungenfibrose vergleichbare Schlüsselrolle der TGF-Wachstumsfaktoren in der Pathogenese der equinen Endometrose konnte nicht eindeutig belegt werden.
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劉國培 and Kwok-pui Lau. "Clinicopathological roles of transforming growth factor alpha (TGFα) in papillary thyroid carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39558733.
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Freese, Christiane. "Rolle der Plasmakonzentrationen von transforming growth factor-[beta]1 [factor-beta1] (TGF[beta]1) [TGF beta 1], Tumor necrosis factor [alpha] [Tumor necrosis factor alpha] (TNF [alpha]) [TNF alpha] und Plasminogen-Activator-Inhibitor-(PAI-)-Antigen bei Patienten mit Diabetes Mellitus Typ 2 und koronarer Herzkrankheit." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=97149200X.
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Mongerard-Coulanges, Medge. "Influence de l'expression du facteur de croissance VEGF sur l'activité antitumorale de l'alendronate." Paris 6, 2009. http://www.theses.fr/2009PA066596.
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Les cellules A431 qui proviennent d’un carcinome épidermique manifestent une résistance transitoire (24h) à l’activité antitumorale de l’alendronate (aminobisphosphonate). Ces cellules ont la particularité de surexprimer le récepteur EGFR (Epidermal Growth Factor Receptor) et produisent son ligand TGF (Transforming Growth Factor Alpha). Cette voie autocrine impliquée dans la prolifération cellulaire ne suffit pas, à elle seule, à expliquer cette résistance. Ce phénomène serait directement lié au niveau d’expression élevé d’un facteur de croissance de l��endothélium vasculaire : VEGF (Vascular Endothelial Growth Factor). Comme beaucoup de cellules tumorales, les cellules A431 expriment des récepteurs à VEGF. VEGF, par des voies autocrines, favorise la survie des cellules A431. De plus, cette étude a montré que VEGF régule la production de TGF par les cellules A431. L’association de l’alendronate et d’un antisens dirigé contre VEGF permet de s’affranchir de ce phénomène de résistance transitoire, permettant une diminution de la production de VEGF par les cellules A431 et une meilleure inhibition de la prolifération cellulaire dès les premières 24h.
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Lautrette, Alexandre. "Interaction entre la voie de l'épidermal growth factor et la voie de l'angiotensine : rôle dans la progression des lésions rénales." Paris 6, 2006. http://www.theses.fr/2006PA066376.
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Deux facteurs de croissance jouent un rôle prépondérant dans le processus lésionnel rénal : l’EGF et l’angiotensine II (AngII). Le but de mon travail de thèse a été d’évaluer si la transactivation du récepteur de l’EGF (R-EGF) était responsable de l’effet délétère de l’AngII lors du développement des lésions rénales, et, si c’était le cas, d’identifier les mécanismes moléculaires à l’origine de ce phénomène. Nous avons montré par des modèles expérimentaux de néphropathie chronique, des lignées de souris génétiquement modifiées et des inhibiteurs pharmacologiques, que les lésions rénales induites par l’AngII passent par l’activation du R-EGF, via la surexpression d’un de ces ligands, le TGF-, elle-même provoquée par l’activation de sa métalloprotéase de clivage, TACE. Puis nous avons débuté l’étude du rôle du TGF- et de sa modulation par la voie de l’AngII dans la pathologie rénale humaine et plus particulièrement dans la polykystose. Nous avons observé une surexpression de TGF- et de TACE dans l’épithélium kystique. L’excrétion urinaire de TGF- est associée à la sévérité de l’insuffisance rénale dans la polykystose et dans différentes néphropathies. Cette excrétion semble dépendre de la prise d’inhibiteur de la voie de l’AngII et être corrélée à une détérioration plus rapide de la fonction rénale. Ceci suggère que le TGF- est impliqué dans le processus lésionnel de diverses néphropathies chroniques humaines et que sa production pourrait être régulée par l’AngII. Ce travail ouvre de nouvelles perspectives dans la recherche de molécules susceptibles de modifier l’évolution des maladies rénales et de traitements capables de ralentir la progression des lésions rénales.
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Maltman, John. "A study of the interactions between macrophage inflammatory protein 1 alpha (MIP-1#alpha#) and transforming growth factor beta (TGF-#beta#) in the control of haemopoietic stem cell proliferation." Thesis, University of Glasgow, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301654.
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Herbert, Brittney-Shea. "Mechanisms of RRR-[alpha]-tocopheryl succinate- and N-(4-hydroxyphenyl)retinamide-induced apoptosis of human HL-60 myelocytic leukemia and MDA-MB-435 breast cancer cells : a role for TGF-[beta] and C-JUN /." Digital version accessible at:, 1998. http://wwwlib.umi.com/cr/utexas/main.
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Perlemuter, Gabriel. "Capside du virus de l'hépatite C et métabolisme lipidique hépatique." Paris 7, 2002. http://www.theses.fr/2002PA077147.
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Bonniaud, Philippe. "Transforming growth factor-β1, connective tissue growth factor et fibrose pulmonaire." Dijon, 2005. http://www.theses.fr/2005DIJOMU01.
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La fibrose pulmonaire (FP) est une maladie incurable. Nous nous sommes intéressés aux effets pathobiologiques de Transforming growth factor (TGF)βsur la FP. Par adénovecteurs, nous avons transféré à des poumons de rongeurs des cytokines susceptibles d'être impliqués dans la FP-TGF-β1, interleukine (IL)-1β, et connective tissue growth factor (CTGF)-. Nous démontrons que :1) TGFβ est essentiel pour l'initiation et la progression de la FP 2)CTGF est nécessaire mais incapable par lui seul d'induire la progression de la FP. CTGF pourrait être un cofacteur de TGFβ 3)FP et emphysème sont dépendants de Smad3, molécule de signal de TGFβ, démontrant l'importance de TGFβ dans l'équilibre entre accumulation et dégradation de matrice 4)la FP induite par IL-1β est dépendante de TGFβ 5)un inhibiteur spécifique du récepteur ALK5 de TGFβ bloque la FP induite par TGFβ. Conclusion : TGFβet ses voies de signal sont clés dans la FP. Ce travail est une ouverture à des possibilités thérapeutiques.
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Norozian, Farnaz. "Transforming Growth Factor-β1 (TGF-β1) Induces Mast Cell Apoptosis." VCU Scholars Compass, 2006. http://scholarscompass.vcu.edu/etd/1544.
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Mast cells are potent effectors of the inflammatory response, playing an important role in atopy, bacterial immunity, and animal models of arthritis, multiple sclerosis, and heart disease. Hence controlling mast cell numbers and responsiveness is essential for preventing inflammatory disease. This work demonstrated that the cytokine TGF-β1 is a potent inducer of mast cell apoptosis, a finding that was consistent for cultured mouse bone marrow-derived mast cells, peritoneal mast cells, and human mast cells. Cell death appeared to be the result of TGF-mediated repression of IL-3 receptor expression and function, leading to mitochondria1 damage and activation of an apoptotic cascade acting via p53 and caspases. While IL-3 receptor expression was reduced within one day of TGF-βl stimulation, apoptosis required at least 3 days to occur. This delay in onset is postulated to allow for protective mast cell effector functions, protecting the host from infection while preventing the establishment of chronic inflammation. These studies support the theory that TGF- β1 is an inhibitor of mast cell survival. Because of the widespread expression of TGF-β1, this cytokine may be an ideal candidate for control of mast cell homeostasis.
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Zuniga, Jorge E. "Binding properties and solution structure of the TGF-[beta] type I receptor extracellular domain : a dissertation /." San Antonio : UTHSC, 2007. http://proquest.umi.com/pqdweb?did=1354133851&sid=1&Fmt=2&clientId=70986&RQT=309&VName=PQD.
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Pan, Dejing. "Transforming growth factor-ß (TGF-ß) signaling in hematopoiesis and tumorigenesis /." Basel : [s.n.], 2008. http://edoc.unibas.ch/diss/DissB_8513.
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Rose, Aidan Michael. "Transforming growth factor-beta signalling in human cutaneous squamous cell carcinoma." Thesis, University of Dundee, 2015. https://discovery.dundee.ac.uk/en/studentTheses/51b1a1c1-ac43-4f60-aa77-9002af3f2186.
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There is an urgent need to define the key pathological driving events in human cutaneous squamous cell carcinoma (cSCC) in order to identify novel therapeutic targets. Already the second most common form of human non-melanoma skin cancer, the incidence of cSCC has continued to rise at epidemic proportions over the past two decades. Rarely, cSCC can be highly aggressive, causing significant soft-tissue defects in sun-exposed areas of skin and progressing to metastatic disease, which is usually associated with poor survival. The transforming growth factor-β (TGF-β) signalling pathway is known to play key regulatory roles in skin homeostasis and wound repair. Murine studies indicate that loss of TGF-β signalling is sufficient to drive cSCC, but conclusive evidence for a similar role in human cSCC remains elusive. Combining immunohistochemical and genetic studies of the TGF-β signalling pathway on human cSCC tissue, with a thorough examination of TGF-β responses in human primary cSCC cell lines in-vitro, this thesis aims to investigate the complex role of TGF-β signalling in human cSCC. An extensive tissue micro-array analysis demonstrated the consistent reduction of endogenous TGF-β signalling activity in human primary cSCC. This intriguingly correlated with higher risk thick tumours pathologically, indicating that TGF-β is likely to act primarily as a tumour suppressor in human cSCC and its reduction or loss may impart a significant growth advantage for cSCC tumour cells. This tumour suppressor effect was reflected in-vitro, whereby the majority of primary cSCC cell lines remained sensitive to TGF-β mediated growth arrest. Resistance to TGF-β tumour suppression was also identified, and mechanistically its main protagonist in cSCC cell lines appeared to be mutational loss of TGF-β receptors. Consolidating in-vitro findings, both whole exome sequencing and 454 pyrosequencing of human cSCC tissue revealed frequent functionally damaging mutations of both TGF-β type 1 and type 2 receptors, indicating that mutational loss of the TGF-β pathway may be a key driving event in human cSCC tumourigenesis. Perhaps most interestingly, mutational loss of TGF-β type 2 receptors in cSCC cell lines appeared to result in a novel pro-oncogenic dependence on TGF-β type 1 receptor kinase activity, highlighting not only the important paradoxical role of TGF-β mediated tumour promotion in cSCC, but also the potential for signalling crosstalk between alternative TGF-β superfamily members, namely Activin signalling, to drive tumourigenesis in the absence of active TGF-β signalling. Although further mechanistic studies are required to support this hypothesis, the mutational status of TGF-β type 2 receptors may not only provide a powerful prognostic tool for patients with cSCC, but also represent an important biomarker for the targeted use of TGF-β inhibitors in potentially aggressive disease where pro-tumourigenic responses could be driving disease progression.
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Gonçalves, Josiane de Oliveira. "Comparação entre os resultados da expressão gênica da desmina, alfa-actina e TGF-beta1 obtidos a partir dos métodos da reação em cadeia de polimerase via transcriptase reversa (RT-PCR) semiquantitativa e em tempo real (qRT-PCR) no modelo." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5141/tde-15082014-163708/.
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Os mecanismos responsáveis pela fibrose hepática na infância são pouco conhecidos. Crianças com atresia das vias biliares, quando submetidas a portoenterostomia a Kasai com sucesso, se tornam anictéricas mas mesmo assim desenvolvem cirrose a longo prazo. Da mesma forma, a ocorrência de estenoses biliares segmentares intra-hepáticas no pós-operatório de transplante hepático podem levar ao desenvolvimento de cirrose em todo o órgão. Tais fatos sugerem que mecanismos endócrinos ou parácrinos estejam envolvidos na fibrogênese hepática. Para elucidar este processo o modelo de ligadura seletiva das vias biliares em ratos jovens foi desenvolvido em nosso laboratório. Usando este modelo, identificamos mudanças na expressão do gene da alfa-actina de músculo liso, tanto no parênquima hepático obstruído como no parênquima hepático adjacente à obstrução. No entanto, o perfil de expressão gênica da desmina, uma proteína presente em níveis elevados durante a ativação das células estreladas hepáticas e o TGF-beta1, principal citocina pró-fibrogênica, não demostraram diferenças significantes quando analisados pelo método do RT-PCR semiquantitativo. Assim, os mecanismos moleculares envolvidos na modulação da fibrogênese hepática nesse modelo experimental não estão totalmente compreendidos. A metodologia do qRT-PCR (PCR em tempo real), têm sido previamente descrita como um método mais preciso e sensível, possibilitando a detecção do aumento do número de cópias do gene à medida que ocorre a amplificação, enquanto que o método do RT-PCR semiquantitativo a análise dos transcritos só é realizada após a etapa da amplificação. O objetivo deste estudo foi avaliar as alterações moleculares no modelo experimental de ligadura seletiva das vias biliares e comparar os resultados obtidos entre os métodos do RT-PCR semiquantitativo e do qRT-PCR em tempo real. Foi realizada a ligadura seletiva do ducto biliar em ratos Wistar com 21 dias de vida, os grupos foram separados de acordo com o momento da morte: 7 ou 60 dias após a cirurgia. A expressão da desmina, alfa actina de músculo liso e TGF-beta1 foi avaliada no tecido do parênquima hepático com obstrução biliar (ducto ligado - DL) e no parênquima hepático adjacente à obstrução biliar (ducto não ligado - DNL) usando o RT-PCR semiquantitativo e o qRT-PCR em tempo real. A metodologia do qRT-PCR em tempo real permitiu identificar mudanças no perfil de expressão gênica que não foram demonstrados pelo método semiquantitativo. O parênquima DL mostrou reação fibrogênica mais intensa, com aumento na expressão da alfa actina de músculo liso e TGF-beta1 após 7 dias. O parênquima DNL apresentou resposta fibrogênica tardia, com aumento da expressão da desmina 7 dias e 60 dias após a cirurgia, além de aumento da alfa-actina de músculo liso 60 dias após a cirurgia. O qRT-PCR em tempo real apresentou maior sensibilidade para identificar mudanças no perfil de expressão gênica em relação ao método convencional do RT-PCR semiquantitativo. Nossos resultados ajudam a esclarecer a dinâmica das alterações moleculares envolvidas na modulação da fibrogênese hepática no modelo experimental de ligadura seletiva do ducto biliar e pode ser diretamente aplicado para o estudo de estenoses biliares intra-hepáticas e atresia das vias biliaresThe mechanisms responsible for liver fibrosis in childhood are poorly understood. Children suffering from biliary atresia, when submitted to the successful Kasai portoentostomy, become anicteric, but nonetheless develop cirrhosis in the long term. Similarly, the occurrence of intrahepatic biliary stenosis in the postoperative period of liver transplantation may lead to cirrhosis of the whole organ. Such facts suggest that endocrine or paracrine mechanisms are involved in hepatic fibrogenesis. To elucidate this process, the selective bile duct ligation model in young rats was developed in our laboratory. Using this model, we identified changes in the expression of smooth muscle alpha-actin both in the obstructed parenchyma and the hepatic parenchyma adjacent to the obstruction. However, the expression profiles of desmin, a protein present at high levels during activation of hepatic stellate cells and TGF-beta1, the main pro-fibrogenic cytokine, were unchanged when analyzed with semiquantitative RT-PCR. Thus, the molecular mechanisms involved in the modulation of hepatic fibrogenesis in this experimental model are not fully understood. The methodology of qRT-PCR (real time PCR) has previously been described as a more precise and sensitive method, allowing the detection of increased copy number of the gene while amplification occurs, whereas by semiquantitative RT-PCR analysis transcripts is only perfomed after the amplification step. This study aimed to evaluate the molecular changes in experimental model of selective bile duct ligation and compare the results between semiquantitative RT-PCR and real-time qRT-PCR methods. Selective biliary duct ligation was performed on Wistar rats with 21 days of life, the groups were separated according to the moment of death: 7 or 60 days after surgery. The expression of desmin, alpha-actin smooth muscle and TGF-beta1 was examined in tissue from hepatic parenchyma with biliary obstruction (duct ligation - DL) and in the adjacent hepatic parenchyma (duct non-ligated - DNL) using semiquantitative RT-PCR and real-time qRT-PCR. The methodology of the real-time qRT-PCR allowed to identify changes in gene expression profile that were not shown by semiquantitative method. The DL parenchyma showed a more severe fibrogenic reaction, with increased alpha-actin smooth muscle and TGF-beta1 expression after 7 days. The DNL parenchyma presented a later fibrotic response, with increased desmin expression 7 and 60 days after surgery, besides of increased alpha-actin smooth muscle 60 days after surgery. Real-time qRT-PCR was more sensitive to identify changes in gene expression profile comparated to the semiquantitative method. Our results help to clarify the dynamic of molecular changes involved in the modulation of hepatic fibrogenesis in an experimental model of selective bile duct ligation and can be directly applied to the study of intrahepatic biliary stenosis and biliary atresia
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Chen, Feng. "Phosphorylation and activation of transforming growth factor beta (TGF-[beta]) receptor kinases." Thesis, Massachusetts Institute of Technology, 1996. http://hdl.handle.net/1721.1/41406.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 1996.On t.p., "[beta]" appears as the lower case Greek letter. Vita.
Includes bibliographical references (leaves 166-207).
by Feng Chen.
Ph.D.
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DUVERNELLE, CATHERINE. "Regulation de l'expression du tgf-1 (transforming growth factor-beta1) dans l'asthme." Université Louis Pasteur (Strasbourg) (1971-2008), 2000. http://www.theses.fr/2000STR13139.
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L'asthme est caracterise, deja a un stade precoce de la maladie, par une fibrose sous-epitheliale et la presence de myofibroblastes, exprimant l'-actine du muscle lisse, dans la muqueuse bronchique. Le tgf-1 (transforming growth factor-1), une cytokine fibrogenique majeure, pourrait etre impliquee dans ces alterations. Afin de determiner si l'expression du tgf-1 est modifiee a un stade precoce du contact avec l'allergene, nous avons developpe un modele d'exposition repetee de patients asthmatiques legers a de faibles doses d'allergene, induisant une hyperreactivite bronchique, sans symptomes d'asthme. Ces inhalations d'allergene induisent une augmentation de l'expression du tgf-1 et du nombre de myofibroblastes dans la muqueuse bronchique de l'asthmatique. Ceci souleve l'hypothese d'un role du tgf-1 dans l'augmentation du nombre de myofibroblastes dans la bronche apres exposition a l'allergene. Dans une deuxieme etape, nous avons etudie la regulation de l'expression du tgf-1 par les glucocorticoides, le traitement majeur de l'asthme, in vivo, chez le patient asthmatique leger a modere, et in vitro, dans les fibroblastes pulmonaires humains en culture primaire. Nous n'avons pas mis en evidence de difference d'expression du tgf-1 dans la bronche de l'asthmatique traite ou non par glucocorticoides inhales. Ceci suggere que l'effet des glucocorticoides sur l'expression du tgf-1 pourrait etre limite dans les voies aeriennes. Les glucocorticoides diminuent l'expression basale ainsi que l'auto-induction du tgf-1 dans les fibroblastes pulmonaires humains en culture. Ils diminuent l'expression d'-actine induite par le tgf-1. Ils pourraient ainsi reduire l'amplification du signal dans la bronche de l'asthmatique. Cet effet n'est toutefois que partiel, montrant des limites a l'action regulatrice des glucocorticoides. En conclusion, l'augmentation de tgf-1 pourrait etre precoce dans l'asthme car elle precede les manifestations cliniques lors de l'inhalation d'allergene et elle pourrait etre impliquee dans l'augmentation du nombre de myofibroblastes dans la paroi bronchique. Nos resultats illustrent egalement la complexite de la regulation de l'expression du tgf-1 dans les voies aeriennes.
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Bailie, Janice Roberta. "The synthesis and biological activity of EFG/TGF-#alpha# fragments." Thesis, Queen's University Belfast, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335455.
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Maurice, Diane Barthelemie Emile. "The role of transforming growth factor-β in thymocyte development and T cell function." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271324.
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Rodgers, Stephen D. "Characterizing the motogenic response of human keratinocytes to epidermal growth factor and transforming growth factor-alpha." Thesis, Massachusetts Institute of Technology, 1996. http://hdl.handle.net/1721.1/40610.
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Köhler, Heike Christine. "Die TGF-[beta] [TGF-beta] vermittelte Suppression der antigenspezifischen Immunantwort kann durch CD28 Kostimulation überwunden werden." München Verl. Dr. Hut, 2008. http://d-nb.info/992163080/04.
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Vo, BaoHan Thi. "Nodal and transforming growth factor-β (TGF-β) signalings in prostate cancer cells." DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2013. http://digitalcommons.auctr.edu/dissertations/500.
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TGF-β signaling pathways contain both tumor suppressor and tumor promoting activities. Nodal, a TGF-β like growth factor, functions as an embryonic morphogen that maintains the pluripotency of embryonic stem cells. We demonstrated that Nodal and its receptors are expressed in prostate epithelial stem cells (WPE) and prostate cancer cells (LNCaP, LNCaP-C8 1, and DU145). Nodal also exerts differential effects on proliferation and migration in different prostate cell lines. First, we determined the comparative effects of Nodal and TGF-β on proliferation and migration under identical experimental conditions in selected prostate cell lines. Our results demonstrated that Nodal and TGF-β exerted similar biological effects on prostate cells; both inhibited proliferation in WPE, RWPE1, and DU145 cells while neither had any effect on the proliferation of LNCaP or PC3 cells. Interestingly, Nodal and TGF-β induced migration in PC3 cells, but not in DU145 cells. TGF-β induced predominantly phosphorylation of Smad3, while Nodal induced phosphorylation of only Smad2. We also determined the expression and differential role of Ski, a co-repressor of Smad2/3, in Nodal and TGF- β signaling in prostate cancer cells. Similar levels of Ski mRNA were found in several established prostate cell lines; however, high levels of Ski protein were only detected in prostate cancer cells and prostate cancer tissue samples. Exogenous Nodal and TGF- β had no effects on Ski mRNA levels. On the other hand, TGF- β induced a rapid degradation of Ski protein mediated by the proteasomal pathway while Nodal had no effect on Ski protein. Reduced Ski levels correlated with increased basal and TGF-β-induced Smad2/3 phosphorylation. Knockdown of endogenous Ski reduced proliferation in DU145 cells and enhanced migration of PC3 cells. We conclude that high levels of Ski expression in prostate cancer cells may be responsible for repression of TGF-β and Smad3 signaling,
but Ski protein levels do not influence Nodal and Smad2 signaling.
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Czubala, Magdalena Anna. "Transforming growth factor-beta (TGF-β) induces HIV-1 restriction in Langerhans cells." Thesis, Cardiff University, 2015. http://orca.cf.ac.uk/77792/.
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Transforming growth factor-beta (TGF-β) drives the development of immature LC from hematopoietic progenitor cells and shapes the cells functions. Here I showed that two LC model cells, MuLC and MDLC, used exchangeably in the research, differ significantly in their phenotype and immune responses. Discrepancies between these models were specifically visible during stimulation with type-I IFN, where MuLC failed to up-regulate ISG levels. Yet both MuLC and MDLC demonstrated low susceptibility to HIV-1 infection, even in the absence of SAMHD-1. This post-entry restriction was conferred by the action of TGF-β on differentiation cells as indicated by our study. Indeed, in the absence of TGF-β supplementation, derived cells showed MDDC phenotype related to high susceptibility of the cells to HIV-1 infection during co-infection with SIV-Vpx. Additionally blocking of the TGF-β signalling, reversed the restrictive phenotype of LC. Importantly this pattern was also confirmed in skin extracted real epidermal LC versus dermal DC, suggesting that SAMHD-1-independent restriction activity operates in TGF-β derived cells. Accordingly to PCR analysis virus replication in LC is interrupted prior to integration, suggesting the role of additional restriction factors at early stages of virus infection or lack of essential viral dependency factors such as dNTPs. Interestingly maturation of MDLC with a synthetic bacterial triacylated lipopeptide or TNF-alpha significantly increased their susceptibility to HIV-1 infection, which may explain why HIV-1 acquisition is increased during co-infection with other STIs. In summary, our study strongly supports the action of SAMHD-1-independent HIV-1 restriction mechanisms in LC. A better understanding of the balance between HIV-1 restriction and propagation from LC to CD4+ T cells may help in the development of new microbicides or vaccines to curb HIV-1 infection at its earliest stages.
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Moore, Lakisha Dionne. "Modulation of Transforming Growth Factor (TGF)-[beta]1 and its implications in breast cancer metastasis." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2008p/ldmoore.pdf.
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Cheung, Ronald Se-Yuen. "Contrasting tumorigenic growth interactions of apoptosis-deficient MYC alleles with Transforming Growth Factor-alpha /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/5000.
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Serwe, Annegret. "Hemmung der Angiogenese und Tumorprogression durch Blockierung der TGF-[beta]-Signaltransduktion [TGF-Beta-Signaltransduktion] durch neue Wirkstoffe isoliert aus Pilzen." Duisburg Köln WiKu, 2007. http://d-nb.info/987489674/04.
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Kariyawasam, Harsha Hemantha. "Airway remodelling and transforming growth factor (TGF)-β superfamily signalling in allergen-induced asthma." Thesis, Imperial College London, 2007. http://hdl.handle.net/10044/1/8641.
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Bronchial biopsies obtained at baseline, 24 hours and 7 days after allergen challenge from mild atopic asthmatics were evaluated to follow the initiation and resolution of allergen-induced inflammation and remodelling in relation to AHR. Further, the expression patterns of the TGF-β Superfamily ligands (TGF-β₁₋₃, activin-A, BMP-2, BMP-4 and BMP-7) and their respective signalling pathway Type II receptors, Type I receptors and signalling Smad proteins were defined in baseline asthma and after allergen provocation in comparision with normal volunteers.
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Karuyawasan, Harsha Hemantha. "Airway remodelling and transforming growth factor (TGF)-B superfamily signalling in allergen-induced asthma." Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497534.
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Frankel, Sara. "The role of transforming growth factor-alpha in the human corpus luteum." Thesis, University of Southampton, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295876.
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White, Robin Elaine. "Manipulation of Astrocytes After Spinal Cord Injury Using Transforming Growth Factor Alpha." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1259160724.
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Zhang, Xuemei. "Src Kinase Signaling Regulates Connective Tissue Growth Factor (CTGF/CCN2) Induction by Transforming Growth Factor-Beta 1 (TGF-b1) in Osteoblasts." Diss., Temple University Libraries, 2010. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/63095.
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AnatomyPh.D.
Connective tissue growth factor (CTGF/CCN2) is a cysteine rich, extracellular matrix protein that acts as an anabolic growth factor to regulate osteoblast differentiation and function. In osteoblasts, CTGF is induced by transforming growth factor beta 1 (TGF-β1) where it acts as a downstream mediator of TGF-β1 induced extracellular matrix production. The molecular mechanisms that control CTGF induction by TGF-β1 in osteoblasts are not understood. We have previously demonstrated the requirement of Src, Erk and Smad signaling for TGF-β1 induced CTGF promoter activity in primary osteoblasts, however the potential interaction among these signaling pathways in osteoblasts remains unknown. In this study, we demonstrate that CTGF is induced by TGF-β1 in rat osteosarcoma osteoblast like cells (ROS17/2.8). TGF-β1 activates Src and blocking of Src family kinases by PP2 abrogates TGF-β1 induced CTGF up-regulation. Western blot analysis revealed that primary osteoblasts and ROS 17/2.8 cells express not only Src, but also other Src family members, such as Fyn, Yes and Hck. In order to determine whether CTGF up-regulation is controlled by Src or other members, we used either kinase-dead dominant negative Src constructs in primary osteoblasts or Src siRNA in ROS17/2.8 cells to block Src function. Inactivation of Src by both kinase-dead and siRNA prevented TGF-β1 induced CTGF induction, demonstrating that TGF-β1 induced CTGF up-regulation is mediated only by Src not by other members. In addition, we also demonstrated that Erk is activated by TGF-β1 and that blocking of Erk activation using pharmacological inhibitors, PD98059 and U0126, prevents TGF-β1 induced CTGF induction, demonstrating the requirement of Erk for CTGF induction. These results prompted us to further explore the cross-talk between Src, Erk and Smads in ROS17/2.8 cells. Inhibition of Src using PP2 prevented Erk activation, demonstrating that Src is upstream of Erk. To investigate how Src and Erk regulate the canonical TGF-β1 signaling pathway, including Smad2/3 phosphorylation and nuclear translocation of activated Smads, we treated cells with TGF-β1 in the presence or absence of the Src inhibitor, PP2, or the Erk inhibitors, PD98059 or U0126. PP2 pre-treatment prevented the phosphorylation of Smad2/3 at both the SSXS motif and the linker region and consequently blocked their nuclear translocation, demonstrating that Src can regulate Smad signaling. In contrast, the Erk inhibitors did not have any effects on Smad phosphorylation and/or nuclear translocation. To examine whether Erk can modulate Smad signaling indirectly through the activation/ inactivation of required nuclear coactivators/ co-repressors that mediate Smad DNA binding, we used electro-mobility shift assays. These experiments showed that inhibition of Erk activation impaired transcriptional complex formation on the Smad binding element (SBE) and TGF- β responsive element (TRE) of the CTGF promoter, demonstrating that Erk activation is required for SBE and TRE transactivation. Taking together, these data demonstrate that Src is an essential upstream signaling transducer for Erk and Smad signaling in osteoblasts, and that while the Smad and Erk signaling cascades appear to function independent of each other, they are both essential for the formation of a transcriptionally active complex on the CTGF promoter.
Temple University--Theses
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Young, Vicky Jane. "The role of the peritoneum and transforming growth factor β in the aetiology of endometriosis." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/21099.
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Endometriosis is a benign inflammatory disorder, defined by the presence of endometrial tissue outside the uterus with lesions typically found on the pelvic peritoneum in close association with the peritoneal mesothelium. The prevalence of endometriosis is estimated at 6-10% of women of reproductive age and it is associated with chronic pelvic pain, dysmenorrhoea, dyspareunia and infertility. Surgical excision can provide symptom relief, but symptoms recur in up to 75% of surgical cases and available medical treatments have undesirable side effects. New treatments are limited due to our poor understanding of the aetiology of endometriosis. To date, the majority of research has focused on changes within the ectopic endometrial tissue to explain the development of endometriosis lesions, however, there is increasing evidence that the peritoneal mesothelium plays an important role. According to Sampson’s theory of retrograde menstruation, ectopic endometrial cells must first have to attach to the surface of the peritoneum before undergoing invasion, proliferation, and neoangiogenesis. TGF-β1 is an inflammatory growth factor that regulates a variety of cellular functions including; cell adhesion, cell invasion and angiogenesis. Levels of TGF-β1 are increased in the peritoneal fluid of women with endometriosis compared to controls and research using a mouse model of endometriosis has demonstrated TGF-β1-null mice to develop smaller and fewer endometriosis lesions than their wild-type controls. Together these studies suggest that TGF-β1 plays a major role in the development of peritoneal endometriosis lesions and that targeting this pathway may be of therapeutic potential. However the functional role that TGF-β1 plays in peritoneal endometriosis is still unclear. The overall aim of this thesis was to determine if the peritoneal expression of TGF-β and its target genes are disrupted in women with endometriosis and whether this could contribute to the development of endometriosis lesions. Our first aim was to determine if the peritoneum was a source of TGF-β expression and if reception and/or signalling were altered in women with endometriosis. We found that the peritoneal fluid of women with endometriosis contained increased concentrations of TGF-β1 and that peritoneal mesothelial cells adjacent to endometriosis lesions expressed significantly higher levels of TGF-β1 mRNA. Analysis of TGF-β signalling targets within the peritoneum showed that women with endometriosis express significantly higher levels of TGF-β targeted genes associated with tumourigenesis processes including; EMT, invasion and angiogenesis. We next asked if there are changes in the metabolic phenotype of endometriosis lesions and peritoneum in women with endometriosis, similar to the metabolic changes seen in tumour cells. Endometriosis lesions expressed markers of aerobic glycolysis, including HIF-1α, suggesting that lesions may metabolise in a similar fashion to tumours. Furthermore, peritoneum adjacent to endometriosis lesions expressed significantly higher levels of markers of aerobic glycolysis, including HIF-1α, suggesting that the peritoneum may feed forward high-energy lactate, a by-product of glycolysis, to the endometriosis lesions. These observations were supported by significantly increased lactate concentrations within the peritoneal fluid of women with endometriosis that positively correlated with levels of TGF- β1. TGF-β1 was shown to increase expression of glycolysis markers and lactate expression in peritoneal mesothelial cells in-vitro, suggesting TGF-β may regulate this change. We then determined if TGF-β1 was responsible for the change in peritoneal mesothelial cell metabolism by signalling through the ID-HIF-1α pathway. ID proteins are transcription factors, whose expression is regulated by the TGF-β superfamily. We found expression of ID1 mRNA to be increased in the peritoneum of women with endometriosis and that TGF-β1 significantly increased ID1 but decreased ID2 expression in the peritoneal mesothelial cells in-vitro. ID1 siRNA knockdown decreased glycolysis initiator HIF-1α mRNA and ID2 siRNA knockdown increased HIF-1α mRNA and lactate expression, suggesting TGF-β1 regulates mesothelial cell metabolism, at least in part, through the ID pathway. ID transcription factors are also known to regulate VEGF-A expression, therefore we next determined if TGF-β1 induced ID1 and/or reduced ID2 expression in the peritoneum promoted VEGF-A mRNA and protein expression. VEGF-A, a cytokine essential for angiogenesis, was significantly increased in the peritoneal fluid of women with endometriosis and levels positively correlated with TGF-β1. TGF-β1 increased VEGF-A expression in-vitro and siRNA knockdown of ID1 decreased and siRNA knockdown of ID2 increased VEGF-A mRNA and protein expression in the peritoneal mesothelial cell. Lastly we aimed to determine if TGF-β1 induces EMT in peritoneal mesothelial cells. The peritoneum of women with endometriosis expressed higher levels of EMT markers. Exposure of peritoneal mesothelial cells to TGF-β1 in-vitro induced EMT-like changes, including; changes to cell morphology, gene expression and protein localisation. Peritoneal mesothelial cells were more migratory and invasive suggesting that TGF-β1 induced EMT may disrupt the mesothelial cell monolayer allowing ectopic endometrial cells to invade the peritoneal tissue or for peritoneal mesothelial cells to migrate into endometriosis lesions. In summary, the novel data presented in this thesis provides evidence that the pelvic peritoneum and in particular the peritoneal mesothelial cell may play a critical role in the aetiology of peritoneal endometriosis. Expression of TGF-β1 and its transcriptional target genes are dysregulated in the peritoneum of women with endometriosis. TGF-β regulated ID expression may induce changes in cell metabolism and promote neoangiogenesis, prompting peritoneal endometriosis lesion development. Furthermore other TGF-β1 transcriptional targets, such as those involved in EMT, are also altered in the peritoneum of women with endometriosis and may contribute the development and maintenance of lesion formation. These results point to a central role for TGF-β1 expression and signalling in the aetiology of peritoneal endometriosis. Furthermore it is likely that changes within the expression profile and morphology of the peritoneal mesothelial cells contribute to peritoneal lesion formation. Drugs that target these pathways may provide new therapies for women with endometriosis.
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Decologne, Nathalie. "Fibrose pleurale expérimentale : rôle de transforming growth factor (TGF)-β1 et des agents anticancéreux (bléomycine)." Dijon, 2008. http://www.theses.fr/2008DIJOMU07.
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"Les liens entre fibrose et plèvre sont importants. Outre la pleurodèse, volontairement induite ou non, la plèvre viscérale peut être le siège de fibroses massives responsables de fibrothorax à la morbidité lourde. La région sous-pleurale est aussi le point de départ « géographique » de la fibrose pulmonaire idiopathique (FPI) sans qu’aucun lien n’ait été établi jusqu’alors entre les deux. Nous avons développé un modèle de fibrose pleurale, sévère et progressive, induite par le transfert du gène de Transforming Growth Factor (TGF)-β1 aux cellules mésothéliales. L’accumulation de collagène au niveau de la plèvre mais aussi dans la région sous-pleurale y est secondaire à une transformation des cellules mésothéliales en myofibroblastes (transformation mésothélio-fibroblastoïde -TMF-). Ces résultats suggèrent l’implication du mésothélium pleural non seulement dans la fibrose pleurale mais également dans la FPI. Nous avons également étudié le rôle des nanoparticules de carbone (NPs, -carbon black ou noir de fumée-), particules "ultrafines" de la pollution et de la fumée de cigarette, sur le pouvoir fibrosant de la bléomycine (BL), agent cytotoxique connu pour ses effets secondaires fibrosants sur le poumon humain. Nous avons montré que les NPs n’aggravent pas la fibrose pulmonaire induite par la BL alors que la co-administration BL/NPs est nécessaire à l’établissement d’une fibrose pleurale. Cette fibrose est, comme dans le modèle précédent, progressive et caractérisée par un dépôt de collagène au niveau pleural et sous-pleural. Nos travaux in vitro sur culture primaire de cellules mésothéliales nous ont permis de confirmer le rôle clé de ces cellules dans le processus de fibrogenèse. Ce travail novateur sur la fibrogenèse pleurale peut aboutir à terme à des applications thérapeutiques de la fibrose pleurale voire de la FPI en utilisant les cellules mésothéliales comme cible. "Links between pleura and fibrosis are important. Apart from pleurodesis, visceral pleura can be the site of severe fibrosis leading to fibrothorax associated with a high morbidity. Subpleural parenchyma is also the anatomical region of idiopathic pulmonary fibrosis (IPF) initiation although no link has been established between both. We developed a model of severe and progressive pleural fibrosis, induced by adenovirus-mediated gene transfer of Transforming Growth Factor (TGF)-β1 to mesothelial cells. In this model, collagen accumulation within the pleura but also within the subpleural parenchyma is the result of the transformation of mesothelial cells into myofibroblasts (mesothelio-fibroblastoid transformation -MFT-). This suggests the involvement of pleural mesothelium not only in pleural fibrosis but also possibly in IPF. We also studied the role of carbon nanoparticles (CN, carbon black), ultrafine particles found in ambient pollution or cigarette smoke, on fibrosis induced by bleomycin (BL), a cytotoxic agent known for its fibrotic side effects on human lungs. We showed that CN do not worsen BL-induced pulmonary fibrosis whereas BL+CN co-administration is needed to induce pleural fibrosis. This fibrosis is, as in the first model, progressive and characterized by collagen deposition within the pleura and the subpleural parenchyma. Our in vitro work on primary mesothelial cells confirms the key role of these cells in fibrogenesis. This innovative work on pleural fibrogenesis could lead to therapeutic applications for pleural fibrosis and even maybe IPF by using mesothelial cells as target
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Ruf, Doris Anne. "Die Entwicklung der Pankreasfibrose im TGF-beta-1-transgenen Tiermodell." [S.l. : s.n.], 2006. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-57128.
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Richter, Audrey. "Studies on the interaction of the epidermal growth factor receptor with epidermal growth factor and transforming growth factor alpha to aid development of a growth factor antagonist." Thesis, University of Southampton, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387049.
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Wong, Soo Hang 1971. "Characterization of transforming growth factor-beta (TGF-_) receptor profiles on human dermal microvascular endothelial cells." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33041.
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Transforming growth factor-beta (TGF-beta) plays an important role in angiogenesis and wound healing. The major cell type involved in angiogenesis are microvascular endothelial cells. Endoglin, a transmembrane glycoprotein, is highly expressed on vascular endothelial cells and has been shown to bind TGF-beta1 and TGF-beta3 and inhibit TGF-beta-induced responses. Mutation in the endoglin gene has been implicated in hereditary haemorrhagic telangiectasia type 1 (HHT1), a dominantly inherited vascular disorder. The role of endoglin in regulating TGF-beta function in the microvasculature is not well understood. The initial interactions on the cell surface between endoglin and the TGF-beta receptors may be an important mechanism by which endoglin modulates TGF-beta signaling and responses. In this study, we show for the first time that on human microvascular endothelial cells, endoglin forms a heteromeric association with betaglycan, a TGF-beta receptor with which endoglin shares limited homology. This complex formation can occur in both a ligand-dependent and ligand-independent manner. In addition, we demonstrate the occurrence of three higher order complexes which contain endoglin and the TGF-beta type II and/or type I receptors in different numbers or ratios. Our results suggest that endoglin may modulate TGF-beta signal transduction by interacting with betaglycan and the TGF-beta signaling receptors on the cell surface in different ratios.
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Mead, Anna Louise. "Modulation of transforming growth factor beta (TGF beta) and conjunctival scarring after glaucoma filtration surgery." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1444824/.
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The conjunctival wound healing response remains the major barrier to achieving long term intraocular pressure control after glaucoma filtration surgery (GFS). Current anti-scarring agents improve the outcome of surgery but act by causing widespread cell death and can be associated with potentially blinding complications. In addition, some individuals still fail surgery. A more physiological and targeted approach to wound healing control and scarring prevention is required. Of all the growth factors, TGF beta has been shown to play a pivotal role in wound healing throughout the body, and has been identified as a potent stimulant of the scarring process in the eye. Modulation of TGF beta has been highlighted as a possible mechanism by which ocular scarring may be reduced. This thesis has investigated the role of TGF p modulation as a potential anti-scarring strategy in glaucoma surgery. In vitro, I have demonstrated that the anti-TGF beta2 monoclonal antibody, CAT-152, inhibits Tenon's fibroblast collagen production and myofibroblast transformation at physiological concentrations. It appears that these are the key histological changes associated with bleb failure following experimental GFS. In vivo, subconjunctival administration of CAT-152, given at the time of surgery and in the immediate post-operative period, successfully improves surgical outcome, reduces subconjunctival fibrosis and is safe and well tolerated. Isolated post-operative administration of subconjunctival CAT-152 can prevent late bleb failure and prolonged dosing with CAT-152 appears to modulate the long-term scarring response after GFS. In addition, the anti-scarring effects of CAT-152 have compared favourably to one of the gold standard anti-scarring agents in clinical use. Finally, I have shown that antisense oligonucleotides directed against TGF beta may also have a role in the prevention of conjunctival scarring. In summary, the work supports the hypothesis that TGF beta modulation may represent a novel potential anti-scarring strategy in glaucoma surgery.
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Ball, Corbie. "The Role of Transforming Growth Factor Beta Signaling in Inflammation-Dependent Colon Cancer." Diss., The University of Arizona, 2015. http://hdl.handle.net/10150/593463.
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Chronic inflammatory conditions such as Crohn's disease (CD) and Ulcerative colitis (UC) are risk factors for colon cancer. TGFβ has been shown to be dysregulated in colon cancer. Bacteria-induced inflammation is necessary for the induction of colon cancer in TGFβ mouse models. However, the mechanism by which TGFβ regulates the inflammatory response in these models is not well elucidated. It was our thought that we needed to be able to distinguish what was TGFβ dependent and what was inflammation dependent. To do this we created 2 colonies of Smad3 mice. One colony was housed with normal colonic bacteria (Smad3-uninfected animals) and the other colony (Smad3-infected animals) had chronic H. hepaticus infection. As previously seen the Smad3⁻/⁻- infected animals developed colitis and carcinoma (~40%). In the absence of H. hepaticus infection SMAD3 was found to negatively regulate TLR4 expression. This was then exacerbated with the addition of H. hepaticus resulting extreme up-regulation of TLR4 and the downstream effectors IRAK4 and NF-κB in Smad3⁻/⁻-infected colonic tissues. Examination of adaptive immune regulation in this model demonstrated that SMAD3 was necessary for FOXP3 expression in H. hepaticus-infected splenocytes. Loss of SMAD3 resulted in up-regulation of IL17 and reduced iTreg populations. These data demonstrate the important role SMAD3 has in maintaining tolerance to microbial populations through both the innate and adaptive immune systems.
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Herckelrath, Tanja. "Genexpressionsmuster nach Behandlung von Hepatomzellen mit dem Cytokin TGF-beta bzw. mit Tumorpromotoren." [S.l. : s.n.], 2004. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB11482176.
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Nguyen-tat, Marc-Daniel. "Analyse der Auswirkungen von TGF-beta auf den Cadherin-Catenin-Adhäsionskomplex in den epithelialen Karzinomzelllinien SW-480 und MCF-7." [S.l. : s.n.], 2006. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-56542.
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Henning, Kirsten. "TGF-beta induzierte Expression extrazellulärer Matrixproteine durch Herzmuskelzellen der adulten Ratte." Giessen VVB Laufersweiler, 2009. http://geb.uni-giessen.de/geb/volltexte/2009/7319/index.html.
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Lieber, Matthew Joshua. "Immunological Crosstalk between Human Transforming Growth Factor-β1 and the Malaria Vector Anopheles stephensi." Thesis, Virginia Tech, 2005. http://hdl.handle.net/10919/42816.
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The emergence of pesticide-resistant mosquitoes and drug-resistant parasites in the last twenty years has made control of malaria more difficult. One novel strategy to better control malaria is the development and release of transgenic mosquitoes whose enhanced immunity prevents transmission of the parasite to the mammalian host. One candidate effector gene is Anopheles stephensi nitric oxide synthase (AsNOS), whose inducible expression and subsequent synthesis of nitric oxide (NO) limits Plasmodium development in A. stephensi.
In mammals, one of the most potent physiological regulators of NOS gene expression and catalytic activity is transforming growth factor-β (TGF-β). Moreover, human TGF-β can activate Drosophila melanogaster Smads, the proteins responsible for TGF-β signal transduction. We have determined that following a bloodmeal, active human TGF-β1 (hTGF-β1) persists in the midgut of A. stephensi for up to 48 hours. My data demonstrate that the midgut epithelium recognizes hTGF-β1 as an immunomodulatory cytokine. Specifically, induction of AsNOS by hTGF-β1 occurs in the midgut within minutes of bloodfeeding. Moreover, hTGF-β1 limits development of the human malaria parasite Plasmodium falciparum in the midgut. In other experiments, provision of the AsNOS catalytic inhibitor L-NAME partially reverses the effect of hTGF-β1 on Plasmodium development. These results suggest that AsNOS is a target of hTGF-β1 signaling and additional effectors that impact parasite development may be regulated by hTGF-β1 as well.
The fact that hTGF-β1 signals mosquito cells to limit malaria parasite development suggests that there is an endogenous TGF-β signaling network in place. An analysis of the A. gambiae genome database revealed the presence of six TGF-β ligands, including gene duplication in the 60A gene, the first evidence of ligand gene duplication outside of chordates. In addition to five receptors, three Smads were identified in the A. gambiae genome predicted to support TGF-β/Activin- and BMP-like signaling. Midgut epithelial cells and an immunocompetent A. stephensi cell line express all three Smads, confirming that a signaling pathway is in place to support signaling by divergent exogenous and endogenous TGF-β superfamily proteins.
The results presented here provide the first evidence of immunological crosstalk between divergent free living hosts of a single parasite. Further, these results imply that the interface between mammals and the mosquitoes that feed on them provide a unique opportunity for circulating molecules in the blood, including TGF-β and other cytokines, to alter the mosquito immune response.Master of Science
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Cheung, Ho-ki, and 張可琪. "Detection and characterization of transforming growth factor beta (TGF-?) and betaglycan in porcine and human milk." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B29275805.
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Yi, Sheng. "Transforming growth factor beta 1 modulates electrophysiological parameters of vas deferens epithelial cells." Diss., Kansas State University, 2013. http://hdl.handle.net/2097/16898.
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Doctor of PhilosophyDepartment of Anatomy and Physiology
Bruce Schultz
Transforming growth factor β1 (TGF-β1) is a cytokine that reportedly affects the severity of cystic fibrosis lung disease. The goal of this project was to define the effect of TGF-β1 on vas deferens, an organ that is universally affected in male cystic fibrosis patients. In the first study, experiments were conducted using freshly isolated porcine vas deferens epithelial cells. Primary porcine vas deferens epithelial cells exposed to TGF-β1 exhibited a significantly reduced basal transepithelial electrical resistance (Rte). TGF-β1-induced reduction in Rte was prevented by SB431542, a TGF-β receptor I inhibitor, indicating that the effect of TGF-β1 requires the activation of TGF-β receptor I. Western blot and immunohistochemistry results showed the expression of TGF-β receptor I in native vas deferens epithelia, indicating that the impaired barrier function and anion secretion that were observed in cultured vas deferens cells can likely be observed in the native context. Immunohistochemical outcomes showed that TGF-β1 exposure led to loss of organization of tight junction proteins occludin and claudin-7. These outcomes suggest that TGF-β1 impairs the barrier integrity of epithelial cells lining the vas deferens. In a parallel study that employed PVD9902 cells that are derived from porcine vas deferens, TGF-β1 exposure significantly reduced anion secretion stimulated by forskolin, forskolin/IBMX, and 8-pCPT-cAMP, suggesting that TGF-β1 affects downstream targets of the cAMP signaling pathway. Real-time RT-PCR and western blot analysis showed that TGF-β1 exposure reduced both the mRNA and the protein abundance of cystic fibrosis transmembrane conductance regulator (CFTR). Pharmacological studies showed that the inhibitory effect of TGF-β1 on forskolin-stimulated anion secretion was abrogated by SB431542 and attenuated by SB203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor. These outcomes suggest that TGF-β1, via the activation of TGF-β receptor I and p38 MAPK signaling, reduces CFTR expression, and thus impairs CFTR-mediated anion secretion. Outcomes from these studies suggest that, in epithelial cells lining the vas deferens, TGF-β1 exposure leads to an impaired physical barrier and/or reduced anion secretion, which is expected to modify the composition and the maintenance of the luminal environment and thus, is expected to reduce male fertility.