ASIC1a inhibits cell pyroptosis induced by acid‐induced activation of rat hepatic stellate cells

Abstract

The activation of hepatic stellate cells (HSCs) is associated with liver fibrosis, the pathological feature of most forms of chronic hepatic damage, and is accompanied by abnormal deposition of the extracellular matrix (ECM). During the pathological process, acid‐sensing ion channel 1a (ASIC1a), which is responsible for Ca2+ transportation, is involved in the activation of HSCs. It has previously been identified that ASIC1a is related to pyroptosis in articular chondrocytes. However, it remains unclear whether ASIC1a restrains pyroptosis during liver fibrosis. Here, we determined that the levels of pyroptosis‐associated speck‐like protein, gasdermin D, caspase‐1, nucleotide‐binding oligomerization domain (NOD)‐like receptor 3, and apoptosis‐associated speck‐like protein (ASC) decreased, while the level of α‐smooth muscle actin and collagen‐I increased upon introduction of ASIC1a into an acid‐induced model. Inhibition or silencing of ASIC1a and the use of Ca2+‐free medium were able to promote the pyroptosis of activated HSCs, which reduced their deposition. In summary, our study indicates that ASIC1a inhibits pyroptosis of HSCs and that inhibition of ASIC1a may be able to promote pyroptosis to relieve liver fibrosis.

Keywords

• acid‐sensing ion channels
• ASIC1a
• hepatic fibrosis
• hepatic stellate cells
• pyroptosis