Effect of CKIP-1 on hepatocyte apoptosis in nonalcoholic fatty liver disease
10.3760/cma.j.cn112138-20220131-00088
- VernacularTitle:CKIP-1对非酒精性脂肪性肝病小鼠肝细胞凋亡的影响
- Author:
Li LI
1
;
Ping XIE
;
Chunshan BI
;
Tianyou WANG
;
Ning WANG
;
Wenjun LIN
;
Chuan ZHANG
;
Wei AN
;
Yutao ZHAN
Author Information
1. 首都医科大学附属北京同仁医院消化科，北京 100730
- Keywords:
Fatty liver;
Apoptosis;
Casein kinases
- From:
Chinese Journal of Internal Medicine
2023;62(1):43-48
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect and underlying mechanism of casein kinase 2 interacting protein-1 (CKIP-1) on hepatocyte apoptosis in nonalcoholic fatty liver disease (NAFLD).Methods:Experimental study. An NAFLD cell model was established by inducing human hepatoma cell line, HepG 2 cells, with oleic acid (OA). Flag-CKIP-1 expression vector and shRNA-CKIP-1 were transfected into HepG 2 cells. Flow cytometry was used to detect the effect of CKIP-1 on the activity and apoptosis of NAFLD hepatocytes. The levels of apoptosis-related proteins were detected by Western blot. CKIP-1 knockout mice in C57BL/6 back-ground were fed with either standard or high-fat diet for 8 weeks. Apoptosis-related signal proteins in NAFLD hepatocytes were detected by immunohistochemistry. Results:After CKIP-1 was transfected into HepG 2 cells, the degree of OA induced cell liposis was significantly reduced ( P<0.05). Annexin V-FITC/PI flow cytometry showed that CKIP-1 reduced the apoptosis of steatotic hepatocytes. Overexpression of CKIP-1 could significantly inhibit the expression of caspase-3 and caspase-9 and increase the expression of Bcl-2/Bax ( P<0.05). Knockdown of CKIP-1 could increase the expression of caspase-3 and caspase-9 ( P<0.05). CKIP-1 knockout could further increase the expression of caspase-3 and caspase-9 in NAFLD mice ( P<0.01, P<0.05), and further decrease the expression of Bcl-2/Bax ( P<0.05). Conclusion:CKIP-1 inhibited the apoptosis of steatotic hepatocytes by up-regulating the expression of apoptosis inhibitor gene, Bcl-2/Bax, and affecting the proteases, caspase-3 and caspase-9.
