title: Inhibition of acid-sensing ion channel 1a in hepatic stellate cells attenuates PDGF-induced activation of HSCs through MAPK pathway.
abstract: Acid-sensing ion channels (ASICs), a group of Na(+)-selective and Ca(2+)-permeant ligand-gated cation channels, can be transiently activated by extracellular acid. Among seven subunits of ASICs, acid-sensing ion channel 1a (ASIC1a), which is responsible for Ca(2+) transportation, is elevated in response to inflammation, tumor, and ischemic injury in central nervous system and non-neuronal tissues. In this study, we demonstrated for the first time the presence of ASIC1a in rat liver and hepatic stellate cells (HSCs). Furthermore, the expression of ASIC1a was increased in primary HSCs and liver tissues of CCl4-treated rats, suggesting that ASIC1a may play certain role in liver fibrosis. Interestingly, we identified that the level of ASIC1a was significantly elevated in response to platelet-derived growth factor (PDGF) induction in a time- and dose-dependent manner. It was also established that Ca(2+)-transporting ASIC1a was involved in acid-induced injury of different cell types. Moreover, inhibition or silencing of ASIC1a was able to inhibit PDGF-induced pro-fibrogenic effects of activated rat HSCs, including cell activation, de novo synthesis of extracellular matrix components through mitogen-activated protein kinase signaling pathway. Collectively, our studies identified that ASIC1a was expressed in rat liver and HSCs and provided a strong evidence for the involvement of the ASIC1a in the progression of hepatic fibrosis.
authors.affiliation: School of Pharmacy, Anhui Medical University, 81 Mei-shan Road, Hefei, 230032, Anhui, China.
authors.forename: Fan-Rong
authors.initials: FR
authors.lastname: Wu
authors.forename: Chun-Xiao
authors.initials: CX
authors.lastname: Pan
authors.forename: Chao
authors.initials: C
authors.lastname: Rong
authors.forename: Quan
authors.initials: Q
authors.lastname: Xia
authors.forename: Feng-Lai
authors.initials: FL
authors.lastname: Yuan
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Ni
authors.forename: Fei-Hu
authors.initials: FH
authors.lastname: Chen
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D010982:Platelet-Derived Growth Factor; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D062565:Acid Sensing Ion Channels; C568268:Asic1 protein, rat; D010982:Platelet-Derived Growth Factor; D002118:Calcium