Liu Haiying, Dai Linyu, Wang Ming, Feng Fumin, Xiao Yonghong
Department of Epidemiology and Health Statistics, School of Public Health, North China University of Science and Technology, Tangshan, China.
Front Cell Dev Biol. 2021 Sep 17;9:684857. doi: 10.3389/fcell.2021.684857. eCollection 2021.
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 Ca 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/Ca-dependent ERS pathway.
以往研究报道，内质网应激（ERS）可通过钙蛋白酶/半胱天冬酶介导肝星状细胞（HSCs）凋亡。目前，肝星状细胞激活是肝纤维化的重要原因，诱导肝星状细胞凋亡在逆转肝纤维化中发挥着不可替代的作用。因此，探索能够诱导肝星状细胞凋亡的作用机制对于逆转肝纤维化以及临床防治肝炎、肝硬化和肝癌等肝纤维化相关疾病具有重要意义。在本研究中，我们证明了衣霉素（一种新型内质网应激诱导剂）可诱导肝星状细胞凋亡，并增加细胞内钙离子浓度以及内质网应激蛋白GRP78、凋亡蛋白半胱天冬酶-12和Bax的表达，同时降低抗凋亡蛋白Bcl-2的表达。我们的研究结果表明，衣霉素可通过钙蛋白酶-2/钙依赖性内质网应激途径诱导肝星状细胞凋亡。
