title: Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets.
abstract: Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activityin vitroand in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells (HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.
authors.affiliation: Chong-Yang Zhang, Jia-Hui Lei, Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
authors.forename: Chong-Yang
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Chong-Yang Zhang, Jia-Hui Lei, Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
authors.forename: Wei-Gang
authors.initials: WG
authors.lastname: Yuan
authors.affiliation: Chong-Yang Zhang, Jia-Hui Lei, Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
authors.forename: Pei
authors.initials: P
authors.lastname: He
authors.affiliation: Chong-Yang Zhang, Jia-Hui Lei, Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Lei
authors.affiliation: Chong-Yang Zhang, Jia-Hui Lei, Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
authors.forename: Chun-Xu
authors.initials: CX
authors.lastname: Wang
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000378:metabolism; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018450:Disease Progression; D005235:Fatty Liver, Alcoholic / Q000150:complications; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D060588:LIM Domain Proteins / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications; D000077185:Resveratrol; D012552:Schistosomiasis / Q000150:complications; D015398:Signal Transduction; D013267:Stilbenes / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D014315:Triterpenes / Q000627:therapeutic use; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D014777:Virus Diseases / Q000150:complications; D000097245:Ursolic Acid
chemical_list: D000101:Acetyl-CoA C-Acetyltransferase; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D035683:MicroRNAs; D000077185:Resveratrol; D013267:Stilbenes; D014315:Triterpenes; D014580:Ursodeoxycholic Acid; D000097245:Ursolic Acid; C464565:MYDGF protein, human; C490351:TGFB1I1 protein, human; C081331:24-norursodeoxycholic acid; C506639:ACAT1 protein, human
keywords: Etiology; Fibrosis; Hepatic stellate cells; Liver cirrhosis; Pathology; Treatment