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

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Abstract

Acid-sensing ion channels (ASICs), a group of Na+-selective and Ca2+-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 Ca2+ 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 Ca2+-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.

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Acknowledgments

This project was supported by the China National Science Foundation Grants (No. 81100301, 81271949).

Conflict of Interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. School of Pharmacy, Anhui Medical University, 81 Mei-shan Road, Hefei, 230032, Anhui, China

    Fan-rong Wu, Chun-xiao Pan, Chao Rong, Quan Xia, Jie Tang, Xiao-yu Wang, Nan Wang, Wen-lin Ni & Fei-hu Chen

  2. Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

    Quan Xia

  3. Department of Pharmacy, The Third Hospital Affiliated to Nantong University, Wuxi, Jiangsu, China

    Feng-lai Yuan

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  1. Fan-rong Wu
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  2. Chun-xiao Pan
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  10. Fei-hu Chen
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Correspondence to Fei-hu Chen.

Additional information

Fan-rong Wu and Chun-xiao Pan contributed equally to this work.

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Wu, Fr., Pan, Cx., Rong, C. et al. Inhibition of acid-sensing ion channel 1a in hepatic stellate cells attenuates PDGF-induced activation of HSCs through MAPK pathway. Mol Cell Biochem 395, 199–209 (2014). https://doi.org/10.1007/s11010-014-2125-0

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