Wang Tao, Wang Qian-Qian, Pan Gui-Xia, Jia Guo-Rong, Li Xiao, Wang Chao, Zhang Li-Ming, Zuo Chang-Jing
Department of Nuclear Medicine, Changhai Hospital, Second Military Medical University Shanghai 200433 China
Department of Marine Biotechnology, Faculty of Naval Medicine, Second Military Medical University Shanghai 200433 China
RSC Adv. 2018 Sep 4;8(54):30950-30956. doi: 10.1039/c8ra03679a. eCollection 2018 Aug 30.
Acid-sensing ion channel 1a (ASIC1a), as a member of the proton-gated cation channel family, can be activated by low extracellular pH, and takes part in many acidity-associated physiopathological processes. However, whether ASIC1a is expressed in human pancreatic stellate cells (PSCs) and involved in acid-induced physiopathological events has not been reported yet. In this study, we investigated the expression of ASIC1a in PSCs and its possible role in the activation and autophagy of PSCs evoked by extracellular acid. Our results show that ASIC1a is present in PSCs, and an enhanced expression of ASIC1a occurs under acid stimuli. More importantly, the activation and autophagy of PSCs can be induced in acidic medium, and inhibition of ASIC1a by ASIC1a-specific blocker psalmotoxin-1 (PcTx1) or siRNA knockdown could suppress these two acid-associated processes. Collectively, our present study reports for the first time that ASIC1a is expressed in PSCs, and provides evidence for the involvement of ASIC1a in the acidic microenvironment-induced activation and autophagy of PSCs.
酸敏感离子通道1a（ASIC1a）作为质子门控阳离子通道家族的一员，可被细胞外低pH激活，并参与许多与酸度相关的生理病理过程。然而，ASIC1a是否在人胰腺星状细胞（PSC）中表达以及是否参与酸诱导的生理病理事件尚未见报道。在本研究中，我们调查了ASIC1a在PSC中的表达及其在细胞外酸诱发的PSC激活和自噬中的可能作用。我们的结果表明，ASIC1a存在于PSC中，并且在酸刺激下ASIC1a表达增强。更重要的是，酸性培养基可诱导PSC的激活和自噬，而ASIC1a特异性阻滞剂蜂毒明肽-1（PcTx1）或通过小干扰RNA敲低ASIC1a可抑制这两个与酸相关的过程。总的来说，我们目前的研究首次报道ASIC1a在PSC中表达，并为ASIC1a参与酸性微环境诱导的PSC激活和自噬提供了证据。
