Inhibition of autophagy reverses alcohol-induced hepatic stellate cells activation through activation of Nrf2-Keap1-ARE signaling pathway

Biochimie
Zheng-Yuan XieFen-Fen Wang

Abstract

Numerous documents have indicated a critical role of autophagy in alcoholic liver fibrosis (ALF), but few papers have reported its function in hepatic stellate cells (HSCs) activation. The current study aimed to investigate the regulation effect of autophagy in HSCs activation, in further to explore the underlying mechanism involved. HSC-T6 cells were treated with ethanol, 3-MA (autophagy inhibitor) or rapamycin (autophagy inducer), and cells were also transfected with si-Nrf2 or si-Keap1. Moreover, ALF animal model was established and Nrf-2(-/-), Keap1 (-/-) mice were purchased. The level of autophagy, the expression of α-SMA and CoL1A1, and Nrf2 antioxidant response were evaluated in stellate cells and livers. Ethanol treatment in cultured cells increased autophagy, oxidative stress level and promoted HSCs activation. Inhibition of autophagy reversed alcohol-induced HSCs activation and suppressed HSCs oxidative stress. Nrf2-Keap1-ARE pathway was involved in HSCs activation and oxidative stress regulated by autophagy. In addition, through in vivo study, we found that inhibition of autophagy could alleviate alcoholic fatty liver injury in ALF model mice and Nrf2 signaling was involved in autophagy regulated HSCs activation. The...Continue Reading

Citations

Oct 17, 2019·International Journal of Molecular Sciences·Shengmin YanXiao-Ming Yin
Oct 18, 2020·Antioxidants·Marina Galicia-MorenoJuan Armendariz-Borunda
Oct 18, 2020·Disease Models & Mechanisms·Lozan SheriffPatricia F Lalor
Feb 16, 2021·World Journal of Hepatology·Elias KouroumalisDimitrios N Samonakis
Jul 7, 2021·Expert Review of Gastroenterology & Hepatology·Shiyun PuHoufeng Zhou

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