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primary topic: Endothelial regulation of liver fibrosis

Endothelial regulation of liver fibrosis
type: Article
abstract: Liver fibrosis is a scarring process of the liver in response to sustained liver injury and can progress into cirrhosis, hepatocellular carcinoma (HCC) and liver failure as end stage disease. Moreover, liver fibrosis dictates the long-term prognosis and mortality in non-alcoholic steatohepatitis (NASH) patients. Parenchymal liver cells such as hepatocytes and non-parenchymal liver cells such as hepatic stellate cells (HSC) and endothelial cells (EC) are involved in liver fibrogenesis. Liver sinusoidal endothelial cells (LSEC) are a discontinuous endothelium exhibiting fenestrations and lacking a basement membrane and form the capillary bed of the liver. Sinusoidal capillarization leads to the activation of HSC, which in turn produce extracellular matrix (ECM) proteins resulting in liver fibrosis. Therefore, the physiological differentiation of LSEC is crucial for liver homeostasis and identification of molecules crucial for the homeostasis of LSEC is indispensable. Recently, we identified transcription factor GATA4 as a master regulator of LSEC differentiation. LSEC-specific loss of GATA4 leads to sinusoidal capillarization and perisinusoidal liver fibrosis in Gata4LSEC-KO mouse. We wondered, if endothelial GATA4 plays a regulatory role in the development of liver fibrosis. Therefore, the aim of this study was to establish two different liver fibrosis models and to analyze the role of GATA4 in the development of liver fibrosis. Chronic toxic carbon tetrachloride (CCl4) model was compared with diet-induced liver fibrosis NASH models. Gata4 was rather increased in endothelial cells of mice with bridging peri-central liver fibrosis in the CCl4 model, whereas downregulation of endothelial Gata4 was seen in the choline-deficient l-amino acid-defined (CDAA) diet-induced NASH model with perisinusoidal liver fibrosis. Downregulation of Gata4 in LSEC of CDAA fed mice was accompanied with sinusoidal transdifferentiation of mLSEC and downregulation of GATA4 dependent genes. Th…
date: 2022
author list: authors
type: EPrint
type: DoctoralThesisEPrint
is part of: repository
has document: Endothelial regulation of liver fibrosis (PDF)
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subject: 570 Biowissenschaften, Biologie

Endothelial regulation of liver fibrosis (PDF)
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has file: Dissertation_SinaKürschner.pdf
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Sina Wietje Kürschner
type: Person
given name: Sina Wietje
family name: Kürschner

Endothelial regulation of liver fibrosis (Other)
type: Document
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Endothelial regulation of liver fibrosis (Other)
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Endothelial regulation of liver fibrosis (Other)
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Endothelial regulation of liver fibrosis (Other)
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Endothelial regulation of liver fibrosis (Other)
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HTML Summary of #31928 Endothelial regulation of liver fibrosis
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primary topic: Endothelial regulation of liver fibrosis

570 Biowissenschaften, Biologie
type: Concept
preferred label: 570 Life sciences @en