@article{APS11232,
author = {Yue-qin Zhu and Li-li Wang and Zi-hao Li and Shi-shun Qian and Zhou Xu and Jin Zhang and Yong-hu Song and Xue-sheng Pan and Na Du and Amira Abou-Elnour and Lynn Jia Tay and Jing-rong Zhang and Meng-xue Li and Yu-xian Shen and Yan Huang},
title = {Acid-sensing ion channel 1a promotes alcohol-associated liver disease in mice via regulating endoplasmic reticulum autophagy},
journal = {Acta Pharmacologica Sinica},
volume = {46},
number = {4},
year = {2025},
keywords = {},
abstract = {Alcohol-associated liver disease (ALD) is a hepatocyte dysfunction disease caused by chronic or excessive alcohol consumption, which can lead to extensive hepatocyte necrosis and even liver failure. Currently, the pathogenesis of ALD and the anti-ALD mechanisms have not been fully elucidated yet. In this study, we investigated the effects of endoplasmic reticulum autophagy (ER-phagy) in ALD and the role of acid-sensing ion channel 1a (ASIC1a) in ER stress-mediated ER-phagy. A mouse model of ALD was established using the Gao-Binge method and the AML12 cell line treated with alcohol was used as an in vitro model. We showed that ASIC1a expression was significantly increased and ER-phagy was activated in both the in vivo and in vitro models. In alcohol-treated AML12 cells, we showed that blockade of ASIC1a with PcTx-1 or knockdown of ASIC1a reduced alcohol-induced intracellular Ca2+ accumulation and ER stress. In addition, inhibition of ER stress with 4-PBA reduced the level of ER-phagy. Furthermore, knockdown of the ER-phagy receptor family with sequence similarity 134 member B (FAM134B) alleviated alcohol-triggered hepatocyte injury and apoptosis. In conclusion, this study demonstrates that alcohol activates ER stress-induced ER-phagy and liver injury by increasing ASIC1a expression and ASIC1a-mediated Ca2+ influx, providing a novel strategy for the treatment of ALD.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/11232}
}