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.

中文翻译：

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ASIC1a抑制由酸诱导的大鼠肝星状细胞活化诱导的细胞凋亡。

肝星状细胞（HSC）的激活与肝纤维化有关，肝纤维化是大多数形式的慢性肝损伤的病理特征，并伴有细胞外基质（ECM）的异常沉积。在病理过程中，酸感应离子通道1a（ASIC1a）负责Ca ²⁺运输，参与了HSC的激活。以前已经确定ASIC1a与关节软骨细胞的焦磷酸化有关。但是，尚不清楚ASIC1a是否在肝纤维化期间抑制发烧。在这里，我们确定了与热解相关的斑点样蛋白，加德明D，半胱天冬酶1，核苷酸结合寡聚域（NOD）样受体3和凋亡相关的斑点样蛋白（ASC）的水平降低了，而将ASIC1a引入酸诱导模型后，α-平滑肌肌动蛋白和I胶原的水平增加。抑制或沉默ASIC1a和使用Ca ²⁺不含培养基的培养基能够促进活化的HSC的热解，从而减少其沉积。总而言之，我们的研究表明ASIC1a抑制HSC的热凋亡，而抑制ASIC1a可能能够促进热凋亡减轻肝脏纤维化。