Endoplasmic reticulum stress-induced apoptosis up-regulation of DR5 via a CHOP-dependent mechanism in HSC-T6 cells
10.12092/j.issn.1009-2501.2020.02.007
- VernacularTitle: 内质网应激通过C/EBP同源蛋白调控死亡受体5对肝星状细胞凋亡的影响
- Author:
Jiali XIE
1
Author Information
1. Department of Pharmacy, The Second People's Hospital of Wuhu
- Publication Type:Journal Article
- Keywords:
C-Jun N-terminal kinase;
C/EBP homologous protein;
Death receptor 5;
Endoplasmic reticulum stress;
Hepatic stellate cell
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2020;25(2):159-166
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the inhibitory effects of endoplasmic reticulum stress(ERS) and TRAIL on hepatic stellate cells in vitro and how their interaction affect the apoptosis of hepatic stellate cells. METHODS: Take thapsigargin (TG) as the endoplasmic reticulum stress-inducing agents, ursodeoxycholic acid (UDCA) for the endoplasmic reticulum stress inhibitors, SP600125 as a c-Jun N-terminal kinase(JNK) inhibitor, HSC-T6 cells were divided into normal control group, DMSO group, TRAIL group, TG group, UDCA group, siCHOP group and SP600125 group. The apoptosis rate of HSC-T6 cell was detected by flow cytometry. Small interference RNA was applied to silence C/EBP homologous protein(CHOP) gene. The protein expression levels of Caspase-8 were detected by immunohistochemistry method. The ERS marker protein CHOP and TRAIL receptor DR5 expression levels were determined by RT-PCR and Western blot. RESULTS:TG (1 μmol/L, 2 μmol/L, 4 μmol/L, 8 μmol/L, 16 μmol/L) increased cell apoptosis rate of HSC-T6. RT-PCR and Western blot showed that the endoplasmic reticulum stress protein marker CHOP could induce the upregulation of TRAIL receptor DR5 and Caspase-8. Moreover, siCHOP and the JNK inhibitor SP600125 could reduce the expression of DR5 and Caspase-8 in HSC cells. CONCLUSION: These results indicated that CHOP and JNK may be a potential factor regulating DR5 expression, and play an important role in the process of apoptosis of hepatic stellate cells.
