title: Inhibition of ASICs reduces rat hepatic stellate cells activity and liver fibrosis: an in vitro and in vivo study.
abstract: Hepatic fibrosis is a chronic inflammation-associated disease, which is involved in the infiltration of inflammatory cells and releasing of proinflammatory cytokines. In the pathological process, protons are released by damaged cells and acidosis is considered to play a critical role in cell injury. Although the underlying mechanism (s) remain ill-defined, ASICs (acid-sensing ion channels) are assumed to be involved in this process. The diuretic, amiloride, is neuroprotective in models of cerebral ischemia, a property attributable to the inhibition of central ASICs by the drug. However, the effect of inhibition of ASICs by amiloride in the liver fibrotic process remains unclear. We found that amiloride (25, 50, or 100 μM) could restrain acid-induced HSCs at pH6 in vitro. In vivo experiments showed that amiloride could significantly alleviate liver injury, decreasing levels of profibrogenic cytokines, collagen deposition, and reducing pathological tissue damage. In summary, amiloride inhibits hepatic fibrosis in vivo and in vitro, which is probably associated with the downregulation of ASICs.
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Chun-xiao
authors.initials: CX
authors.lastname: Pan
authors.forename: Fan-rong
authors.initials: FR
authors.lastname: Wu
authors.forename: Xiao-yu
authors.initials: XY
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Wen-fan
authors.initials: WF
authors.lastname: Gao
authors.forename: Jin-fang
authors.initials: JF
authors.lastname: Ge
authors.forename: Fei-hu
authors.initials: FH
authors.lastname: Chen
mesh_terms: D062646:Acid Sensing Ion Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D062565:Acid Sensing Ion Channels / Q000737:chemistry / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000584:Amiloride / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D062646:Acid Sensing Ion Channel Blockers; D062565:Acid Sensing Ion Channels; D000199:Actins; D000410:Alanine Transaminase; D000584:Amiloride; D001219:Aspartate Aminotransferases; D002251:Carbon Tetrachloride; D003094:Collagen; D016207:Cytokines; D053503:Epithelial Sodium Channels; C498862:Acta2 protein, rat
keywords: ASICs; activation; amiloride; hepatic stellate cells; liver fibrosis