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Inhibition of hepatic damage and liver fibrosis by brain natriuretic peptide
Authors:Takuhiro Sonoyama  Kazutoshi Miyashita  Kwijun Park  Naofumi Oyamada  Daisuke Taura  Megumi Inuzuka  Yasutomo Fukunaga  Masakatsu Sone  Kazuwa Nakao
Affiliation:Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
Abstract:Anti-fibrotic and organ protective effects of brain natriuretic peptide (BNP) have been reported. In this study, effects of BNP on liver fibrosis were examined in the carbon tetrachloride (CCl4)-induced liver fibrosis model using BNP-transgenic (Tg) and wild-type (WT) mice. Twice-a-week intraperitoneal injections of CCl4 for 8 weeks resulted in massive liver fibrosis, augmented transforming growth factor (TGF)-β1 and type I procollagen α1 chain (Col1a1) mRNA expression, and the hepatic stellate cell (HSC) activation in WT mice, all of which were significantly suppressed in Tg mice. These observations indicate that BNP inhibits liver fibrosis by attenuating the activation of HSCs.
Keywords:BNP, brain natriuretic peptide   CCl4, carbon tetrachloride   Tg, transgenic   WT, wild-type   TGF, transforming growth factor   Col1a1, type I procollagen α1 chain   HSC(s), hepatic stellate cell(s) NP, natriuretic peptide   ANP, atrial natriuretic peptide   CNP, C-type natriuretic peptide   GC, guanylyl cyclase   ROS, reactive oxygen species   CYP2E1, cytochrome P450 2E1   NASH, non-alcoholic steatohepatitis   SMA, smooth muscle actin   DMN, dimethylnitrosamine
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