NDLI: Inhibition of acid-sensing ion channel 1a in hepatic stellate cells attenuates PDGF-induced activation of HSCs through MAPK pathway

Content Provider	Springer Nature Link
Author	Wu, Fan rong Pan, Chun xiao Rong, Chao Xia, Quan Yuan, Feng lai Tang, Jie Wang, Xiao yu Wang, Nan Ni, Wen lin Chen, Fei hu
Copyright Year	2014
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 CCl$_{4}$-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.
Starting Page	199
Ending Page	209
Page Count	11
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	395
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Springer US
Publisher Date	2014-06-18
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Acid-sensing ion channels Hepatic fibrosis Hepatic stellate cells MAPK pathway Biochemistry Medical Biochemistry Oncology Cardiology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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