Дисертації з теми "KLFs factor"
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Alhashem, Yousef. "ROLES OF KRÜPPEL LIKE FACTORS KLF1, KLF2, AND KLF4 IN EMBRYONIC BETA-GLOBIN GENE EXPRESSION." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1880.
Повний текст джерелаWilliams, Helen. "Investigation of the metabolic functions of Klf3 and Klf8 using mouse models." Thesis, The University of Sydney, 2011. https://hdl.handle.net/2123/28935.
Повний текст джерелаCrutchfield, Gerald L. "Kruppel-Like Transcription Factor 6 & 7 mRNAs (KLF6 & KLF7) Expression in the Developing Zebrafish." University of Akron / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=akron1572200378181869.
Повний текст джерелаCurtis, Benjamin. "KLF2/KLF4 Double Knock-out Mouse Embryos Show Cranial Bleeding with Endothelial Disruption of the Primary Head Vein." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2216.
Повний текст джерелаAlhashem, Yousef N. "REGULATION OF THE MOUSE AND HUMAN β-GLOBIN GENES BY KRÜPPEL LIKE TRANSCRIPTION FACTORS KLF1 AND KLF2". VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/2927.
Повний текст джерелаVinjamur, Divya. "The Roles of Krüppel-like Transcription Factors KLF1 and KLF2 in Mouse Embryonic and Human Fetal Erythropoiesis." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/630.
Повний текст джерелаPandya, Ashka Y. "Structural and functional analysis of KLF4." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2009r/pandya.pdf.
Повний текст джерелаJiang, Wen. "KLF4 and retinoid receptor signaling in cancer." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2009. https://www.mhsl.uab.edu/dt/2009r/jiang.pdf.
Повний текст джерелаLiu, Zhaoli. "KLF4 regulates notch1 expression and signaling during epithelial transformation." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2006. https://www.mhsl.uab.edu/dt/2008r/liu.pdf.
Повний текст джерелаSaum, Keith L. "Targeting Endothelial Kruppel-like Factor 2 (KLF2) in Arteriovenous Fistula Maturation Failure." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1530269382206163.
Повний текст джерелаHUDDLESON, JUSTIN PHILIP. "REGULATION OF THE KLF2 TRANSCRIPTION FACTOR GENE IN ENDOTHELIAL CELLS BY FLUID SHEAR STRESS." University of Cincinnati / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1140098308.
Повний текст джерелаSchlunk, Christian Verfasser], and Lothar [Akademischer Betreuer] [Kanz. "The role of Krüppel-Like Factor 4 in Human Gastric Cancer Development and Progression and Comparison of the context dependent role of KLF4 and KLF5 in carcinogenesis / Christian Schlunk ; Betreuer: Lothar Kanz." Tübingen : Universitätsbibliothek Tübingen, 2013. http://d-nb.info/1160601496/34.
Повний текст джерелаXiong, Ye. "KLF2: A Kruppel like Family Transcription Factor in Myeloid Cells Negatively Regulates Th2 Response." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1445343045.
Повний текст джерелаMohamad, Safa. "The Roles of Krüppel-Like Factor 1 (KLF1) in the Human Fetal Erythroid Compartment." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/587.
Повний текст джерелаLi, Tianshu. "Identification of Epithelial Stromal Interaction 1 and Epidermal Growth Factor Receptor as Novel Kruppel-Like Factor 8 Targets in Promoting Breast Cancer Progression." Doctoral diss., University of Central Florida, 2013. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/6311.
Повний текст джерелаPh.D.
Doctorate
Molecular Biology and Microbiology
Medicine
Biomedical Sciences
Leclère, Pierre. "Rôle du facteur de transcription circadien Krüppel-Like Factor 10 (KLF 10) dans le développement des complications hépatiques de l’obésité." Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2019. http://theses.univ-cotedazur.fr/2019AZUR6030.
Повний текст джерелаNon-alcoholic steatohepatitis (NASH), the progressive form of nonalcoholic fatty liver diseases (NAFLDs), is a global public health problem without approved pharmacological therapy. NAFLD extend from non-pathogenic lipid accumulation, known as hepatic steatosis to hepatocellular carcinoma (HCC) through a wide spectrum of stages including NASH and fibrosis. NASH is featured by hepatic inflammation and hepatocyte cell death. Better understand NASH pathogenic cellular and molecular mechanisms is an important clinical requirement.Circadian timing system (CTS) is the main synchronizer of organismal physiology to environmental light/dark cycles. This CTS is comprised of a central pacemaker in the supra-chiasmatic nucleus of the hypothalamus and peripheral clocks localized in each single cell throughout the brain and body. Western society life style, including junk food consumption and erratic feeding, chronic jet lag, light exposure at night and shift-work, can disrupt the CTS. CTS disruption has been assessed as a risk factor for the development of chronic diseases including metabolic syndrome and cancer. The liver is the most rhythmic organ and evidence for an intricate link between CTS disruption and NAFLD development is most illustrated by (i) the genetic and environmental disruption of the CTS leads to dyslipidemia, hepatic steatosis as well as spontaneous NASH and HCC development (ii) the circadian hepatic transcriptome is rearranged in mice fed high fat diet and displaying hepatic steatosis, showing that metabolic disruption also impacts diurnal oscillation of transcripts. Krüppel-like factor 10 is a circadian transcription factor directly regulated by the circadian clock in the liver and help shaping the hepatic diurnal transcriptome and the control carbohydrate and lipid metabolism homeostasis. Beside from metabolism, this transcription factor has also been shown to regulate two NASH related processes, in very different contexts, namely inflammation and cell death. We thus aimed to evaluate the implication of circadian rhythms and the role of KLF10 during steatohepatitisHere, we show that hepatic steatosis and inflammation display diurnal rhythmicity in mice developing steatohepatitis upon feeding with a methionine and choline deficient diet (MCDD). Core clock gene oscillations remained mostly unaffected but rhythmic Klf10 expression was abolished in this model. Klf10 deficient mice (Klf10-/-) display enhanced liver injury despite the same level of hepatic steatosis and inflammation that control mice upon MCDD challenge. Specific genetic ablation of Klf10 only in hepatocytes phenocopied the phenotype of Klf10-/- mice upon MCDD. Silencing Klf10 in isolated primary hepatocytes also sensitized these cells to apoptosis along with increased caspase 3 activation in response to TNFα. We also show that the hepatic KLF10 expression correlates with liver injury (ALT activity) and the circulating keratin 18 hepatocyte death marker in a cohort of obese patients. Collectively our findings suggest that specific NASH features including steatosis and inflammation display diurnal oscillations and the associated altered circadian expression of Klf10 may aggravate liver injury through hepatocyte sensitization to cell death.Collectively, our results gathered from cellular and animal experiments as well as correlative study in Human indicate that hepatic steatosis and inflammation could be rhythmic during NASH and that KLF10 could be a hepatoprotective factor that could limit NAFLD progression
Tsoi, Lai-shan, and 蔡麗珊. "Tumor suppressive functions of Krüppel-like factor 4 (KLF 4) in neuroblastoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hdl.handle.net/10722/208425.
Повний текст джерелаpublished_or_final_version
Surgery
Master
Master of Philosophy
Bell, Kristin N. "The Role of Krupple-like Factor 5 in Normal Intestinal Homeostasis." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470753836.
Повний текст джерелаYori, Jennifer L. "Discerning The Role Of Krüppel-Like Factor 4 In Breast Cancer." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1295636538.
Повний текст джерелаSun, Xiaoguang, Biji Mathew, Saad Sammani, Jeffrey R. Jacobson, and Joe G. N. Garcia. "Simvastatin-induced sphingosine 1−phosphate receptor 1 expression is KLF2-dependent in human lung endothelial cells." SAGE PUBLICATIONS INC, 2017. http://hdl.handle.net/10150/623874.
Повний текст джерелаALBOSLEMY, TALIB. "Kruppel-like factor 2: A regulator of macrophage-mediated innate immune response against Staphylococcus aureus biofilm." Kent State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1523544938448141.
Повний текст джерелаAndreoli, Verónica. "Análisis funcional del factor de transcripción KLF6 en el control de la proliferación celular : interacción con oncoproteínas celulares y virales." Strasbourg, 2010. https://publication-theses.unistra.fr/restreint/theses_doctorat/2010/ANDREOLI_Veronica_2010.pdf.
Повний текст джерелаThe mammalian Krüppel-like factor 6 (KLF6) is involved in critical roles such as growth-related signal transduction, cell proliferation and differentiation, development, apoptosis and angiogenesis. Additionally, KLF6 appears to be an emerging key factor during cancer development and progression. Its expression is thoroughly regulated by several celldamaging stimuli. The aim of this thesis was to characterize the biochemical signals that regulate the function of KLF6 and analyze their effects on cell proliferation and apoptosis. We first characterized the role of JNK and p38 signal transduction pathways in the expression and function of KLF6. Then we studied the effects of KLF6 in response to cellular stress generated by UV radiation and analyzed their effects on the c-Jun onco-protein and on apoptosis. Finally, we determined the effects of KLF6 in the context of cellular stress generated by infection with adenovirus that is able to induce cell proliferation or apoptosis
Russo, Lucia. "Papel del factor de transcripción Kruppel-like factor 2 en la disfunción endotelial hepática asociada a la hipertensión portal y al daño por isquemia y reperfusión." Doctoral thesis, Universitat de Barcelona, 2011. http://hdl.handle.net/10803/79037.
Повний текст джерелаDiab, Thoria. "Role of the 3' untranslated region in the post-transcriptionnal regulation of KLF6 gene expression in hepatocellular carcinoma." Toulouse 3, 2013. http://www.theses.fr/2013TOU30202.
Повний текст джерелаKrüppel-like factor 6 (KLF6) is a tumor suppressor gene that is involved in the regulation of cell cycle, cellular proliferation, differentiation and cell death by apoptosis. KLF6 expression is altered in liver carcinogenesis. However, little is known on the mechanisms governing KLF6 expression in HCC. In the current study, we asked whether 3’UTR may be responsible for down regulation of KLF6 mRNA in HCC. Our results demonstrated that KLF6 mRNA half-life was greatly decreased in cells derived from HCC. Moreover, 3'UTR strongly inhibited the activity and expression of the reporter gene. In addition, we found that most of KLF6 3’UTR destabilisation activity resides between nucleotides 1835 and 2615
Moore, Darcie Leann. "Transcriptional Control of Axon Growth Ability." Scholarly Repository, 2010. http://scholarlyrepository.miami.edu/oa_dissertations/639.
Повний текст джерелаYang, Cheng-Tao. "Manipulating transcription factors in human induced pluripotent cell-derived cells to enhance the production and the maturation of red blood cells." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28928.
Повний текст джерелаDoddaballapur, Anuradha [Verfasser], Stefanie [Akademischer Betreuer] [Gutachter] Dimmeler, and Amparo [Gutachter] Acker-Palmer. "Regulation of endothelial metabolism by laminar shear stress and flow-induced transcription factor KLF2 / Anuradha Doddaballapur. Betreuer: Stefanie Dimmeler. Gutachter: Stefanie Dimmeler ; Amparo Acker-Palmer." Frankfurt am Main : Universitätsbibliothek Johann Christian Senckenberg, 2016. http://nbn-resolving.de/urn:nbn:de:hebis:30:3-403510.
Повний текст джерелаDoddaballapur, Anuradha Verfasser], Stefanie [Akademischer Betreuer] [Gutachter] [Dimmeler, and Amparo [Gutachter] Acker-Palmer. "Regulation of endothelial metabolism by laminar shear stress and flow-induced transcription factor KLF2 / Anuradha Doddaballapur. Betreuer: Stefanie Dimmeler. Gutachter: Stefanie Dimmeler ; Amparo Acker-Palmer." Frankfurt am Main : Universitätsbibliothek Johann Christian Senckenberg, 2016. http://d-nb.info/1104252341/34.
Повний текст джерела伊藤, 源士, 好孝 関戸, 範恭 宇佐美, 好規 長谷川, 洋. 吉岡 та 薫. 下方. "Kruppel-like factor6(KLF6)の非小細胞肺癌における分子生物学的検討". 日本肺癌学会, 2002. http://hdl.handle.net/2237/10952.
Повний текст джерелаGutierrez-Aguilar, Ruth. "Etudes génétiques des gènes de la famille KLF : analyse fonctionnelle d'un variant du promoteur de KLF11." Lille 2, 2007. http://www.theses.fr/2007LIL2S019.
Повний текст джерелаLiefold, Nicola. "A new role of transcription factor SOX17 as potential interaction partner of KLF4 and EGR-1 in human coronary artery smooth muscle cells and in differentiating mouse ES-cells." Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-73311.
Повний текст джерелаDavis, Reed. "Expression of Kruppel-like factors 6 & 7 in Central Visual Structures of Adult Zebrafish Following Optic Nerve Crush." University of Akron / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=akron1518006256589223.
Повний текст джерелаGivelet, Maëlle. "Étude des cellules souches germinales : caractérisation des cellules souches germinales humaines et effets de l'hypoxie Transcriptional landscape of spermatogonial stem cells and progenitors in human spermatogenesis Impact of hypoxia on the proliferation and colony-formation capacity of SSCs in culture Spermatogonial stem cells and progenitors are refractory to reprogramming to pluripotency by the transcription factors Oct3/4, c-Myc, Sox2 and Klf4." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB038.
Повний текст джерелаThroughout life, sperm cells are produced from germinal stem cells (GSCs) during the process of spermatogenesis in the testis. GSCs have the ability to self-renew to maintain stem cell stock and to differentiate. Male infertility is responsible in one out of two cases of issues of procreation. In patients treated with radiotherapy and/or chemotherapy (particularly in children with cancer), one of the major side effects that affects the quality of life after healing is the attrition of the GSCs stock and the subsequent problems of infertility. The most severe infertility issue, the Sertoli-Cell-Only syndrome with a complete germ cell aplasia, results from the exhaustion of the GSCs population. Therapeutic solutions such as transplantation of GSCs obtained from testicular biopsies harvested prior to cancer treatments are being studied. Recent studies on testicular transplantation of GSCs in non-human primates have shown the restoration, in the sterilized animal, of spermatogenesis allowing in vitro fertilization of oocytes by intracytoplasmic microinjection of spermatozoa derived from transplanted GSCs. These very encouraging results bring for the first time the transplantation of GSCs into the field of preclinical application. However, the identity of the pool of human GSCs and the molecular mechanisms governing their self-renewal remain poorly known. My thesis work focused on the characterization of GSCs in humans. During this project I also used the mouse model of GSCs to better understand some mechanisms of the physiological regulation of GSCs. As a first step, this thesis work has contributed to define, using a combination of cell markers and the testicular transplantation, as functional test, a population of immature spermatogonia enriched in GSCs. The specific expression profile of this population was performed by transcriptomic analysis, and allowed us to define a transcription regulator network preferentially expressed in this population. Among the enriched transcriptional regulators in the human immature spermatogonia population, we focused on the study of the bHLH transcriptional repressor Hes1 in the murine model. Under serum and growth factors-deprived conditions of culture inducing proliferative arrest and quiescence, our study tends to show a protective role of HES1 against cell death. In addition, we also observed a decrease in the number of cells with the potential to regenerate spermatogenesis in GSCs cultures when Hes1 expression is decreased. Secondly, we studied the effect of hypoxia on the self-renewal and differentiation of murine GSCs in culture. Indeed, hypoxia is an important component of the stem cell niche that regulates their cell fate. We observed that high hypoxia (1% and 0.1% oxygen) has a deleterious effect on the ability of murine GSCs to form colonies, and moderately induce quiescence and the onset of differentiation of GSCs. A positive effect on the functionality of murine adult GSCs has been observed at 3.5% oxygen, but these conditions do not support the proliferation and maintenance at long-term of human GSCs. Finally, this work has contributed to a better understanding of the mechanisms responsible for the spontaneous reprogramming to pluripotency of GSCs in vitro. While Yamanaka factors are effective for reprogramming testicular somatic cells, they do not allow reprogrammation of adult GSCs and spermatogonial progenitors. These results suggest the existence of a specific mechanism preventing reprogramming by Yamanaka factors of adult germ cells into a pluripotent state
Diakiw, Sonya. "Characterisation of the role of KLF5 in normal haemopoiesis and acute myeloid leukaemia." Thesis, 2011. http://hdl.handle.net/2440/68839.
Повний текст джерелаThesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science and School of Paediatrics and Reproductive Health, 2011
Wong, Chui-Wei, and 黃翠薇. "Study gene regulation of telomerase by transcription factor KLF4 in stem cells." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/01366240947350365009.
Повний текст джерела國立臺灣大學
微生物學研究所
98
The zinc finger Kruppel-like transcription factor 4 (KLF4) has been implicated in cancer formation and stem cell regulation. However, the function of KLF4 in tumorigenesis and stem cell regulation are poorly understood due to limited knowledge of its targets in these cells. In this study, we have revealed a surprising link between KLF4 and regulation of telomerase, which offers important insight into how KLF4 contributes to cancer formation and stem cell regulation. KLF4 sufficiently activated expression of the human telomerase catalytic subunit, hTERT, in telomerase-low ALT and fibroblast cells, while down-regulation of KLF4 reduced its expression in cancerous and stem cells which normally exhibits high expression. Furthermore, KLF4-dependent induction of hTERT was mediated by a KLF4 binding site in the proximal promoter region of hTERT. In human embryonic stem cells, expression of hTERT replaced KLF4 function to maintain their self-renewal. Therefore, our findings demonstrate that hTERT is one of the major targets of KLF4 in cancer and stem cells to maintain long-term proliferation potential.
Passaro, Fabiana. "Klf5 transcription factor is required to maintain mouse embryonic stem cell pluripotency." Tesi di dottorato, 2008. http://www.fedoa.unina.it/2713/1/Passaro_Genetica.pdf.
Повний текст джерелаMiranda, Andrea Lis. "El factor de transcripción KLF6 regula la proliferación, fusión y migración de las células trofoblásticas." Doctoral thesis, 2021. http://hdl.handle.net/11086/19513.
Повний текст джерелаRESUMEN La placenta es un órgano temporal clave durante el embarazo ya que ejerce la conexión entre la madre y el feto por lo que su correcta formación y funcionamiento es fundamental para el bienestar fetal y el progreso del embarazo. El desarrollo temprano de la placenta humana se considera, en algunos aspectos, similar a la carcinogénesis. Ambos se desarrollan en un ambiente con bajos niveles de oxígeno, su desarrollo es modulado por el sistema inmunológico, la expresión de protooncogenes, microARNs y genes supresores tumorales. Además, las células placentales y tumorales tienen una alta capacidad para proliferar, fusionarse, migrar e invadir. La principal diferencia entre la progresión del cáncer y el desarrollo de la placenta es que, en esta última, estos procesos están estrictamente regulados. La desregulación de algunos de estos procesos se asocia con complicaciones del embarazo como preeclampsia, retardo del crecimiento intrauterino, placentas cretas, entre otras. Durante el desarrollo placentario las células progenitoras de la placenta, los citotrofoblastos (CTB), proliferan rápidamente y comienzan a diferenciarse, algunas para dar origen por fusión celular al sinciciotrofoblasto (STB) multinucleado y algunas hacia el trofoblasto extravelloso migratorio y altamente invasivo que permite anclar la placenta al útero materno. KLF6 es un factor de transcripción ubicuo con un dominio de transactivación ácido N-terminal y un dominio de unión al ADN tipo dedos de zinc C-terminal. KLF6 es altamente expresado en la placenta. Los ratones Klf6-/- mueren en el día embrionario 12,5 mostrando deterioro del desarrollo de la placenta. Previamente, se demostró que KLF6 es necesario para la fusión célula-célula en cultivos primarios de citotrofoblastos vellosos (CTBv), así como en la línea celular BeWo derivada de trofoblasto y modula la expresión de la proteína inhibidora del ciclo celular p21, de sincitina-1 (Syn-1) y de la subunidad β de la gonadotrofina coriónica humana (β-hCG). Además, la inmunoreactividad de KLF6 es mayor en el lecho placentario de las placentas provenientes de embarazos con preeclampsia que en las de los embarazos sin complicaciones. Sin embargo, se desconoce el mecanismo por el cual KLF6 regula la diferenciación del CTBv y no existen reportes sobre el rol de KLF6 en el proceso de migración e invasión de los citotrofoblastos extravellosos (CTBev). En contextos tumorales, KLF6 actúa como un gen supresor de tumores. De hecho, la disminución en los niveles de KLF6 aumenta la tumorigenicidad y la metástasis en numerosos tipos de cáncer. No obstante, también se ha informado el efecto contrario en células normales y cancerosas. En esta tesis se estudió el mecanismo por el cual KLF6 participa en la diferenciación de los CTBv los cuales fusionan para formar el STB. Se demostró que KLF6 es suficiente para desencadenar la fusión de células BeWo. Además, KLF6 incrementó la expresión de moléculas importantes involucradas en este proceso, entre ellas β-hCG, Syn-1 y p21, y disminuyó la proliferación celular. Mientras que, una mutante de KLF6 que carece del dominio ácido, implicado en la actividad transcripcional (KLF6Δac), disminuyó la sincicialización in vitro de cultivos primarios de CTBv, así como, la expresión de Syn-1 y β-hCG. Además, la fusión celular desencadenada por KLF6 se redujo en células silenciadas para p21. Estos resultados sugieren que KLF6 induce la sincicialización de CTBv a través de un mecanismo que involucra su dominio regulador de la transcripción de una manera dependiente de p21. Por otro lado, se demostró que KLF6 está involucrado en la diferenciación del CTBev. La disminución en la expresión de KLF6 o la sobreexpresión de la mutante carente del dominio acídico (KLF6Δac) incrementó la migración, la actividad de la metaloproteinasa 9 y la expresión de moléculas importantes involucradas en la migración y la transición epitelio-mesenquimal (EMT), como β-catenina, conexina-43, integrinas α5 y β1. Además, provocó cambios morfológicos compatibles con la EMT confirmados por estudios de microscopía de fuerza atómica y Raman. En línea con los datos obtenidos in vitro, se demostró que placentas cretas, caracterizadas por ser anormalmente invasivas, poseen niveles de inmunomarcación para KLF6 más bajos con mayor localización citoplasmática en comparación con placentas normales. Los resultados obtenidos en esta tesis sugieren que KLF6 es un regulador maestro de la diferenciación celular en la vía sincicial y que su dominio de transactivación N-terminal es necesario para esta función. Mientras que, en la diferenciación de los CTBev, KLF6 actúa regulando negativamente la migración a través de la modulación de la expresión de moléculas importantes involucradas en este proceso. En resumen, los resultados actuales permiten proponer a KLF6 como un regulador clave de la diferenciación del trofoblasto a través de la vía vellosa y extravellosa, y sugieren que la desregulación en su nivel de expresión o la pérdida de su actividad transcripcional contribuiría al desarrollo de patologías como preeclampsia y placentas cretas.
ABSTRACT The placenta is a key temporary organ during pregnancy. It establishes critical relationships between the mother and the fetus, so its correct formation and functioning is essential for fetal well-being and the outcome of the pregnancy. Early human placental development resembles carcinogenesis in otherwise healthy tissues. The placental and tumor development share numerous features. Both take place in an environment with low levels of oxygen, their development is modulated by the immune system and the expression of protooncogenes, microRNAs and tumor suppressor genes. Furthermore, placental and tumor cells have a high capacity to proliferate, fuse, migrate and invade. The main difference between cancer progression and placenta development is the tight regulation of these processes in the placenta. However, the dysregulation of these processes is associated with pregnancy complications such as preeclampsia, intrauterine growth restriction and placentas cretas, among others. During development, placental progenitor cells, the cytotrophoblasts (CTB), rapidly proliferate and begin to differentiate, some towards the villous pathway to form the multinucleated syncytiotrophoblast (STB) by cell-cell fusion and some towards the highly invasive and migratory extravillous trophoblasts (EVT) that anchor the placenta to the uterus. KLF6 is a ubiquitous transcription factor with an N-terminal acidic transactivation domain and a C‐terminal zinc finger DNA-binding domain. KLF6 is highly expressed in placenta. Klf6-/- mice die at day E12.5 showing impaired placenta development. Previously, it was demonstrated that KLF6 is required for cell–cell fusion in primary culture of human villous cytotrophoblasts (vCTB) isolated from term placenta, as well as in the BeWo trophoblast-derived cell line and it modulates the expression of the cell cycle inhibitory protein p21, syncytin-1 (Syn-1), and the β subunit of the human chorionic gonadotropin (β-hCG). Additionally, KLF6 immunoreactivity is higher in the placental bed of preeclamptic pregnancies than in those of uncomplicated pregnancies. However, the mechanism by which KLF6 regulates CTBv differentiation is unknown and there are no reports about the role of KLF6 in the process of migration and invasion of the EVT. In cancer, KLF6 acts mainly as a tumor suppressor gene. Indeed, KLF6 knockdown increases the tumorigenicity and metastasis in numerous types of cancer. Nevertheless, the opposite effect has been also reported in normal and cancer cells. In this thesis, the mechanism by which KLF6 participates in CTB differentiation through the villous and extravillous pathways was explored. It was demonstrated that KLF6 is sufficient to trigger cell fusion and to increase the expression of important molecules involved in this process, such as β-hCG, Syn-1 and p21, in addition, it downregulates cell proliferation. Furthermore, a KLF6 mutant lacking the acidic domain involved in its transcriptional activity (KLF6Δac) impaired the in vitro syncytialization of villous trophoblast cells isolated from human term placentas and decreased Syn-1 and β-hCG expression. Moreover, cell fusion triggered by KLF6 was reduced in cells silenced for p21. These results suggest that KLF6 induces vCTB syncytialization through a mechanism that involves its regulatory transcriptional domain in a p21-dependent manner. Additionally, the KLF6 involvement in EVT differentiation was established. The decrease in KLF6 expression or the overexpression of the transcriptionally inactive mutant (KLF6Δac) increase cell migration, metalloproteinase 9 activity, and the expression of molecules involved in migration and epithelial mesenchymal transition (EMT) such as β-catenin, connexin-43, integrin α5 and β1. In addition, it causes morphological changes consistent with EMT, confirmed by atomic force microscopy and Raman studies. In line with the data obtained in vitro, it was shown that placentas cretas, characterized by being abnormally invasive, have lower KLF6 immunostaining levels and more cytoplasmic localization compared to normal placentas. The results obtained in this thesis suggest that KLF6 is a master regulator of cell differentiation into the syncytial pathway and that its N-terminal transactivation domain is required for this function. While in EVT differentiation, KLF6 negatively regulates migration by modulating the expression of important molecules involved in this process. In summary, current results allow proposing KLF6 as a key regulator of trophoblast differentiation through the villous and extravillous pathways and suggest that dysregulation in its expression level or the loss of its transcriptional activity may contribute to the development of pregnancy pathologies like preeclampsia and placentas cretas.
2023-07-31
Fil: Panzetta de Dutari, Graciela María Del Valle. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina.
Fil: Panzetta de Dutari, Graciela María del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina.
Fil: Miranda, Andrea Lis. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Fil: Caputto, Beatriz Leonor. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; Argentina.
Fil: Caputto, Beatriz Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina.
Fil: Genti de Raimondi, Susana Del Valle. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina.
Fil: Genti de Raimondi, Susana Del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina.
Fil: Vivas, Laura Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.
Fil: Varone, Cecilia L. Universidad Nacional de Buenos Aires; Argentina.
Fil: Varone, Cecilia L. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina.
Wang, Angela, and 王安姬. "Regulation and Signaling Mechanisms of Shear Stress-induced Thrombomodulin and Transcription Factor KLF2 in Endothelial Cells." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/90838029392621564952.
Повний текст джерела國立臺灣大學
化學工程學研究所
94
During atherogenesis, inflammation plays an important role. Thrombomodulin (TM), in vascular endothelial cells, has anti-coagulation and anti-inflammation properties. Transcription factor, Kruppel-like factor 2 (KLF2) has been shown to participate in the regulation of the expression of TM and endothelial nitric oxide synthase and thus is important for regulating thrombotic function. Endothelial cells are constantly under the influence of flow-induced hear stress and the atherosclerotic lesions are closely related to this hemodynamic effect. In the present study, we focused on the study of gene expression of TM and KLF2 in endothelial cells exposed to shear stress. Human umbilical vein endothelial cells (HUVECs) and bovine aortic endothelial cells (BAECs) were used to probe into the signaling mechanisms involved in this shear-induced TM and KLF2 expression. ECs exposed to shear stress of 25 dyn/cm2 transiently induced the TM mRNA expression with peak induction about 1.6-folds after exposure to shear stress for 4 to 6 hrs before it returned to basal level. However, KLF2 mRNA expression in those ECs was found to be a sustained one with peak induction more than 85-folds. While mRNA expression of TM and KLF2 were significantly induced in shear-induced ECs, protein expression of TM and KLF2 had no obvious increase. Furthermore, TM mRNA and KLF2 mRNA were significantly increased in ECs exposed to higher shear stress (25 dyn/cm2) in contrast to those ECs exposed to low shear stress (4.5 dyn/cm2) indicating that TM mRNA induction is sensitive to shear force. However, the protein expression of TM and KLF2 from shear-treated ECs show no significant difference as compared to those control ECs. This indicates that protein stability may be involved in those shear-treated ECs. ECs under shear flow condition constantly release nitric oxide (NO). The role of NO in this shear-induced TM and KLF2 mRNA expression was examined. ECs exposed to a NO donor (NOC18) significantly suppressed the TM and KLF2 mRNA level with a dose-dependent manner. Consistently, shear stress to ECs increased the TM promoter activity. Interestingly, ECs pretreated with an eNOS inhibitor (L-NAME) did not enhance the shear-induced TM promoter activity. Furthermore, the protection effect of shear flow on cytokine-treated ECs was examined. ECs treated with tumor necrosis factor (TNF) greatly reduced the TM and KLF2 expression. ECs pretreated with TNF followed with shear flow, however, significantly attenuated the TNF-induced suppression of TM mRNA levels. In contrast, the basal KLF2 and the shear-induced KLF2 mRNA levels were not affected by TNF pretreatment. In summary, shear flow to ECs increases the TM and KLF2 mRNA expression in a dose-dependent manner. However, this induction can not be reflected by the TM protein levels indicating that the stability of TM mRNA and protein may be involved. Furthermore, shear flow exerts its protective effect by attenuating the TNF-induced suppression of TM mRNA expression. ECs treated with NO suppress the TM and KLF2 mRNA expression. Although the detailed up-regulation mechanism of TM remains unclear, this study suggests that shear flow plays an important role in regulating TM expression and consequently affects endothelial integrity.
Milanovic, Maja [Verfasser]. "The role of transcription factors Klf4 and Icsbp in the development of myeloid cells / vorgelegt von Maja Milanovic." 2006. http://d-nb.info/988936968/34.
Повний текст джерелаIdrissa, Moussa Mohamed. "Études structurales d’interactions protéine/protéine impliquées dans la leucopoïèse." Thèse, 2017. http://hdl.handle.net/1866/18660.
Повний текст джерелаHematopoietic development is regulated through a combinatorial interplay between lineage-specific activators and the general transcription factors that enables cell-specific patterns of gene expression. In this study, the transcription factors KLF2 and KLF4 play crucial roles in lymphocytes B and T development by activating transcription of specific genes through interactions with the co-activator (CBP). These interactions involve the transactivation domains (TAD) localized in the N-terminal region of KLF2 and KLF4 factors. Previous studies have shown that TADs are also found in the tumor suppressor protein p53 and these TADs are responsible for the interactions between the p53 protein and the coactivator CBP. Recently, several structures of p53TADs in complex with the TAZ2 and KIX domains of CBP have shown that these TADs are acidic and possess a ΦΧΧΦΦ motif crucial for the formation of the interaction. Interestingly, these TADs are similar to the ones found on KLF2 and KLF4. This thesis provides a structural and functional characterization of the interactions formed by the transcription factors KLF2 and KLF4, which have opposing roles, and competes for the same interacting partner CBP to activate transcription. The analysis is done using isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) spectroscopy and a yeast activation assay. This study brings a greater understanding on the opposing roles yet complementary of KLF2 and KLF4 proteins involved in B and T lymphocytes specific lineages selection and also provides information for potential therapeutic research regarding disease such as leukemia.
Chen, Chih-Chen, and 陳志榮. "The Correlation of Expression of Kruppel-like factors (KLF) and the Clinical Manifestations of the Breast Cancer." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/09760283469531534642.
Повний текст джерела臺北醫學大學
臨床醫學研究所
97
Breast cancer is the fourth cause of female cancer deaths in Taiwan with increased incidence and young age tendency (age?T40 years old, 29.3%). In recent years, the distinct age distribution and more aggressive clinical behavior in the young patient are noted in Taiwanese women and this phenomenon is different from that in the Western countries. Besides, due to the heterogeneity of breast cancer, designation of an ideal treatment protocol for breast cancer could not only be based on the traditionally histological, clinical, and biological markers (such as ER, PR and HER-2/neu) but also some new prognostic factors. Therefore, the specific study of breast cancer in Taiwan women becomes an important issue. Kruppel-like factors (KLF) belong to a group of zinc finger like transcription factors and are involved in regulating cell proliferation. KLFs have more than twenty subtypes. The studies of Kruppel-like factors in breast cancer are increased recently and are mainly focused on their roles in tumorigenesis. The KLFs are considered as new prognostic factors in breast cancers in some studies. Among them, KLF4 and KLF5 are most important and are broadly studied, but most studies are mainly in Western countries. In order to provide better treatment strategies for native breast cancers, the aim of this study is to evaluate the correlation of KLF4 and KLF5 expression with pathologic changes and clinical behaviors of breast cancers in Taiwanese women. In the literatures, KLF4 has both tumor suppressor gene and oncogene functions. KLF4 can promote the proliferation of cancer cells and also can regulate production of extracellular matrix. More aggressive clinical manifestations may be associated with the cellular location of KLF4 in cancer cells. The patients have poor prognosis when nuclear localization of KLF4 in cancer cells. KLF5 also has both tumor suppressor gene and oncogene functions. KLF5 can facilitate the proliferation and transformation of cancer cells. Increased expression of KLF5 is a poor prognostic factor and is positively correlated with the expression of HER-2/neu and Ki-67 in breast cancer. KLF5 also has increased expression in breast cancer patients younger than 50 years old. In this study, we used immunohistochemistry method to evaluate both staining intensity and staining pattern of expression of KLF4 and KLF5 in non-tumor and tumor parts (including invasive and in situ cancers) of breast tissues. We also analyzed the associations of expression status of KLF4 and KLF5 with histological features, clinical presentation and other prognostic factors of breast cancer. We enrolled 60 breast cancer patients with the mean age 47 years old and the mean tumor size was 2.7 cm. The clinical presentation was stage I: 30.0%; stage II: 43.3%; stage III: 21.7%; and stage IV: 5.0%. The follow-up period of these patients ranged from 8 to 59 months (mean 27 months) and only one patient died of disease. Pathologically, most of them were invasive ductal carcinoma (IDC) (90.0%) and showed moderately differentiation (66.7%). The accompanied ductal carcinoma in situ (DCIS), if present, was predominantly highest grade (60.0%). The immunohistochemical study of KLF4 in cancer cells showed cytoplasmic and nuclear expression. The intensity of tumor part was stronger than non-tumor part in 43.3% patients. We evaluated the association of the immunohistochemical results of KLF4 and KLF5 and clinical manifestations of these patients. We found that more KLF4 nuclear expression in tumor cells positively correlated with more advanced stage (p=0.006) and larger size of the tumor (size more than 2 cm in maximal diameter, p=0.035). KLF4 expression was also age-related. KLF4 intensity was stronger in tumor part than non-tumor part in patients older than 50 years old (p=0.007) and, in this setting, the invasive cancer tended to be poorly differentiated (p=0.033). Besides, consistent expression of KLF4 between DCIS and invasive cancers was also found: stronger intensity in DCIS accompanied with stronger intensity in invasive cancers (p=0.002), more predominant nuclear expression in DCIS with more predominant nuclear expression in invasive cancers (p<0.001). The expression of KLF5 in cancer cells was mainly cytoplasmic. The intensity of tumor part was stronger than non- tumor part in 58.3% patients. For KLF5, invasive breast cancers with negative or weak cytoplasmic expression showed better differentiation compared with strong cytoplasmic expression (p=0.035). Consistent expression of KLF5 between DCIS and invasive cancers was also found: stronger intensity in DCIS with stronger intensity in invasive cancers (p<0.001) and more predominant cytoplasmic expression in DCIS with more predominant cytoplasmic expression in invasive cancers (p<0.001). Moreover, there was no association between the following factors and the KLF4 expression intensity and pattern, respectively: ER (p=0.271 and p=0.925), PR (p=0.191 and p=0.448), HER-2/neu (p=0.136 and p=0.454), p53 (p=1.000 and p=0.925), and p21 (p=0.572 and p=0.367). There was also no correlation between the following factors and the KLF5 expression intensity and staining pattern, respectively: ER (p=1.000 and p=0.512), PR (p=1.000 and p=1.000), and HER-2/neu (p=0.520 and p=0.443). Our study found that KLF4 expression is positive association with tumor stage, tumor size, and age but could not conduct the conclusion that nuclear KLF4 expression was an adverse prognostic factor proposed in the literatures. In the other hand, KLF5 expression was associated with the differentiation of invasive cancers. We also found that KLF5 nuclear localization was mainly restrictedly in non-tumor breast ducts and lobules (16.7%) and loss of nuclear expression in DCIS and invasive cancers, the finding not mentioned in literatures before. Although we didn’t study the biologic function of KLF5, it maybe presented a possible tumor suppressor gene-like function of KLF5. We found that there were associations of KLF4 and KLF5 expressions and clinical manifestations in breast cancers but the expressions of KLF4 and KLF5 were not enough to predict the prognosis and survival rate. The major cause was due to too short follow up period of our patients to exactly evaluate the association of survival rate and expressions of KLF4 and KLF5. Therefore, well-designed retrospective studies with adequate follow up period for studying correlation of expressions of KLF4 and KLF5 and prognosis and survival rate of breast cancers are necessary.
Liefold, Nicola [Verfasser]. "A new role of transcription factor SOX17 as potential interaction partner of KLF4 and EGR-1 in human coronary artery smooth muscle cells and in differentiating mouse ES-cells / vorgelegt von Nicola Liefold." 2007. http://d-nb.info/985547995/34.
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