Abstract
Liver fibrosis is a manifestation of chronic liver injury. It leads to hepatic dysfunction and is a critical element in the pathogenesis of cirrhosis and hepatocellular carcinoma. The activation of hepatic stellate cells (HSC) plays a central role in liver fibrogenesis of different etiologies. To elucidate the molecular mechanism of this phenomenon, it is important to analyze the changes in gene expression that accompany the HSC activation process. In this study, we isolated quiescent and activated HSCs from control mice and mice with CCl4-induced liver fibrosis, respectively, and performed RNA sequencing to compare the differences in gene expression patterns between the two types of HSCs. We also reanalyzed public gene expression data for fibrotic liver tissues isolated from patients with HBV infection, HCV infection, and nonalcoholic fatty liver disease to investigate the gene expression changes during liver fibrosis of these three etiologies. We detected 146 upregulated and 18 downregulated genes in activated HSCs, which were implicated in liver fibrosis as well. Among the overlapping genes, seven transcription factor-encoding genes, ARID5B, GATA6, MITF, PBX1, PLAGL1, SOX4, and SOX9, were upregulated, while one, RXRA, was downregulated. These genes were suggested to play a critical role in HSC activation, and subsequently, in the promotion of liver fibrosis. We undertook the RNA sequencing of quiescent and activated HSCs and analyzed the expression profiles of genes associated with HSC activation in liver fibrotic tissues from different liver diseases, and also aimed to elucidate the changes in gene expression patterns associated with HSC activation and liver fibrosis.
Highlights
Liver fibrosis, which is characterized by the excessive deposition of the extracellular matrix (ECM) in the liver [1], generally occurs in association with chronic liver injury induced by multiple factors, such as chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, alcohol abuse, and nonalcoholic steatohepatitis (NASH) [2, 3]
As hepatic stellate cells (HSC) activation is a common process in liver fibrosis of different etiologies, we speculated that HSC activation may contribute to the changes in the expression patterns of genes commonly linked to HBV, HCV, and nonalcoholic fatty liver disease (NAFLD)-associated liver fibrosis
We undertook the identification of the common genes by reanalyzing the public gene expression data on HBV, HCV, or NAFLD-associated fibrotic liver tissues
Summary
Liver fibrosis, which is characterized by the excessive deposition of the extracellular matrix (ECM) in the liver [1], generally occurs in association with chronic liver injury induced by multiple factors, such as chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, alcohol abuse, and nonalcoholic steatohepatitis (NASH) [2, 3]. HSCs activation-related genes expressed in HBV, HCV and NAFLD associated fibrotic liver tissues. J.H.; 81802423 to C.Q.; 81602067 to L.H. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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