Tunicamycin Induces Hepatic Stellate Cell Apoptosis Through Calpain-2/Ca2 +-Dependent Endoplasmic Reticulum Stress Pathway

Haiying Liu; Linyu Dai; Ming Wang; Fumin Feng; Yonghong Xiao

doi:10.3389/fcell.2021.684857

Tunicamycin Induces Hepatic Stellate Cell Apoptosis Through Calpain-2/Ca^{2 +}-Dependent Endoplasmic Reticulum Stress Pathway

Front Cell Dev Biol. 2021 Sep 17:9:684857. doi: 10.3389/fcell.2021.684857. eCollection 2021.

Authors

Haiying Liu¹, Linyu Dai¹, Ming Wang¹, Fumin Feng¹, Yonghong Xiao¹

Affiliation

¹ Department of Epidemiology and Health Statistics, School of Public Health, North China University of Science and Technology, Tangshan, China.

Abstract

It has been reported that calpain/caspase-mediated apoptosis induced by endoplasmic reticulum stress (ERS) in hepatic stellate cells (HSCs) by previous studies. At present, the activation of HSC is an important cause of liver fibrosis, and the induction of HSC apoptosis plays an irreplaceable role in reversing liver fibrosis. Therefore, it is of great significance to explore mechanisms of action that can induce HSC apoptosis for the reversal of hepatic fibrosis and the clinical prevention and treatment of hepatic-fibrosis-related diseases such as hepatitis, cirrhosis, and liver cancer. In the current study, we demonstrated that tunicamycin (a novel ERS inducer) can induce the apoptosis of HSCs and increase the concentration of intracellular Ca²⁺ and the expression of ERS protein GRP78, apoptosis protein caspase-12, and Bax, while it can decrease the antiapoptosis protein expression of Bcl-2. Our findings indicate that tunicamycin can induce HSCs apoptosis through calpain-2/Ca²⁺-dependent ERS pathway.

Keywords: apoptosis; calpain-2; endoplasmic reticulum stress; hepatic stellate cells; tunicamycin.