title: Bevacizumab attenuates hepatic fibrosis in rats by inhibiting activation of hepatic stellate cells.
abstract: Angiogenesis is a fundamental part of the response to tissue injury, which is involved in the development of hepatic fibrosis. Vascular endothelial growth factor plays an important role in angiogenesis. The expression of VEGF is increased during hepatic fibrogenesis and correlates with the micro-vessel density. In this study, we investigated the effects of bevacizumab, an anti-angiogenetic drug, on the formation of hepatic fibrosis. We found that bevacizumab could attenuate the development of hepatic fibrosis and contribute to the protection of liver function. Bevacizumab was also found to downregulate the expression α-SMA and TGF-β1, which have been reported to be profibrogenic genes in vivo. We also observed that the expression of VEGF increased significantly during the development of hepatic fibrosis and CCl4 was found to induce hepatocytes to secrete VEGF, which led to the activation and proliferation of HSCs. Bevacizumab was also found to block the effects of the hepatocytes on the activation and proliferation of HSCs. Our results suggest that bevacizumab might alleviate liver fibrosis by blocking the effect of VEGF on HSCs. Bevacizumab might be suitable as a potential agent for hepatic fibrosis therapy.
authors.affiliation: Department of Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China ; Department of Hepatobiliary Surgery, Shuguang Hospital, Shanghai, China.
authors.forename: Yangqing
authors.initials: Y
authors.lastname: Huang
authors.forename: Helin
authors.initials: H
authors.lastname: Feng
authors.forename: Tong
authors.initials: T
authors.lastname: Kan
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.forename: Minfeng
authors.initials: M
authors.lastname: Zhang
authors.forename: Yesheng
authors.initials: Y
authors.lastname: Li
authors.forename: Changying
authors.initials: C
authors.lastname: Shi
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
authors.forename: Yunquan
authors.initials: Y
authors.lastname: Luo
authors.forename: Jiamei
authors.initials: J
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use*; D000068258:Bevacizumab; D002251:Carbon Tetrachloride; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D017077:Culture Media, Conditioned; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D002251:Carbon Tetrachloride
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