Hepatic HRC induces hepatocyte pyroptosis and HSCs activation via NLRP3/caspase-1 pathway

被引:0
作者
Jingwen Wu
Mingyu Zhang
Suhong Xia
Ping Han
Kai Zhao
Kaixin Peng
Wangdong Zhou
Dean Tian
Jiazhi Liao
Jingmei Liu
机构
[1] Tongji Hospital of Tongji Medical College,Department of Gastroenterology
[2] Huazhong University of Science and Technology,undefined
来源
Journal of Molecular Medicine | 2022年 / 100卷
关键词
HRC; Pyroptosis; HMGB1; HSC; Liver fibrosis;
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学科分类号
摘要
The histidine-rich calcium-binding protein (HRC) is a regulator of Ca2 + homeostasis and it plays a significant role in liver fibrosis. Pyroptosis, a specific inflammatory cell death, can lead to hepatic stellate cells (HSCs) activation and liver fibrosis. However, the role of HRC in pyroptosis has not been explored. In this study, we demonstrated that HRC, mainly located in the hepatocyte, was over expressed in fibrotic liver tissues. We further found that enforced expression of HRC in hepatocytes induced pyroptosis and HMGB1 release, and subsequently led to HSCs activation by NLRP3/caspase-1 pathway. In addition, the proliferation and migration of HSCs were also enhanced by HRC overexpression in hepatocytes. Furthermore, NLRP3 inhibitor MCC950 and caspase-1 inhibitor VX-765 alleviated hepatic HRC-mediated hepatocytes pyroptosis and HSCs activation. This study demonstrated that hepatic HRC promoted HSCs activation by inducing hepatocyte pyroptosis, which suggests that HRC may be a promising therapeutic target to prevent liver fibrosis.
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页码:1787 / 1799
页数:12
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