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

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.

[Knockdown of calreticulin increases intracellular Ca concentration and promotes apoptosis of HSC-LX2 human hepatic stellate cells].

Objective To investigate the effect of silencing calreticulin (CALR) gene on the apoptosis and intracellular Ca concentration in HSC-LX2 human hepatic stellate cells. Methods Small interfering RNA (siRNA) targeting CALR was designed and transfected into HSC-LX2 cells by lipofectamine transfection, and then the cells with CALR knockdown were screened out. Apoptosis was detected by flow cytometry combined with annexin V-FITC/PI labeling.

CaMK II/Ca2+ dependent endoplasmic reticulum stress mediates apoptosis of hepatic stellate cells stimulated by transforming growth factor beta 1.

Previous studies by our group have demonstrated that the calcium imbalance in rat hepatic stellate cells (HSCs) can induce endoplasmic reticulum stress (ERS) and promote cell apoptosis. KN-62, an inhibitor of Calmodulin kinase II (CaMK II), can decrease the expression of CaMK II that plays a major role in regulating the steady state of intracellular Ca2+. Uridine triphosphate (UTP) plays a biological role in increasing indirectly the level of intracellular Ca2+.