GAS5-inhibited Hepatocyte Pyroptosis Contributes to Hepatic Stellate Cell Inactivation Via MicroRNA-684 and AHR

Overview

Journal iScience

Publisher Cell Press

Date 2023 Aug 2

PMID 37529102

Authors

Zhichao Lang

Rongrong Zhang

Xinmiao Li

Yan Jin

Yuhang Hu

Xinyi Lin

Yunzhi Tang

Jingnan Zhang

Lei Zheng

Zhixian Yu

Jianjian Zheng

Affiliations

Soon will be listed here.

Abstract

Hepatocyte pyroptosis has been shown to be involved in liver damage progression. Previously, we found that growth arrest-specific 5 (GAS5) is a regulator of hepatic stellate cell (HSC) activation. However, whether GAS5 plays a role in hepatocyte pyroptosis remains unclear. In this study, reduced GAS5 was shown in CCl-treated mice and restoration of GAS5-inhibited liver fibrosis . Hepatocyte pyroptosis participated in the effects of GAS5-inhibited liver fibrosis, associated with reduced caspase-1, NLRP3, and IL-1β (hepatocyte pyroptosis markers). Notably, AHR expression, a suppressor of NLRP3, was enhanced by GAS5. Silencing AHR inhibited GAS5-mediated hepatocyte pyroptosis. GAS5 and AHR were targets of microRNA-684 (miR-684). In addition, the effects of GAS5 on hepatocyte pyroptosis could be inhibited by miR-684. Interestingly, GAS5-mediated hepatocyte pyroptosis contributed to HSC inactivation. In conclusion, we demonstrate that GAS5 inhibits hepatocyte pyroptosis and HSC activation, at least in part, via regulation of miR-684 and AHR.

Citing Articles

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