Impacts of FABP4 silencing on endoplasmic reticulum stress and insulin resistance in gestational diabetes mellitus rats by regulating PERK/eIF2α/ATF4/CHOP signaling pathway
10.3969/j.issn.1000-484X.2024.04.006
- VernacularTitle:FABP4沉默通过调节PERK/eIF2α/ATF4/CHOP信号通路对妊娠糖尿病大鼠内质网应激和胰岛素抵抗的影响
- Author:
Zhen LI
1
;
Dongping YU
;
Wu LUO
;
Ting TAO
;
Hui CHEN
;
Ning WANG
Author Information
1. 长沙市第一医院病理科,长沙 410005
- Keywords:
FABP4;
PERK/eIF2α/ATF4/CHOP signaling pathway;
Gestational diabetes mellitus;
Endoplasmic reticulum stress;
Insulin resistance
- From:
Chinese Journal of Immunology
2024;40(4):705-713
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the impacts of fatty acid binding protein 4(FABP4)silencing on endoplasmic reticulum stress(ERS)and insulin resistance(IR)in gestational diabetes mellitus(GDM)rats by regulating protein kinase R-like endoplasmic reticulum kinase(PERK)/eukaryotic initiation factor 2α(eIF2α)/transcription factor 4(ATF4)/C/EBP homologous protein(CHOP)signaling pathway.Methods:GDM rat model was established by intraperitoneal injection of streptozotocin(STZ).Rats were injected with FABP4 siRNA plasmid(si-FABP4),negative control plasmid(NC)and PERK activator(CCT020312)via tail vein,and were randomly grouped into Normal group,GDM group,GDM+NC group,GDM+si-FABP4 group and GDM+si-FABP4+CCT020312 group.The levels of FABP4,blood lipids,inflammatory markers and oxidative stress markers in pancreatic tissue were detected,the expres-sions of PERK/eIF2α/ATF4/CHOP signaling pathway-related proteins in pancreatic tissue were detected.HTR-8/SVneo cells were divided into 5 groups:Control group,high glucose(HG)group,HG+NC group,HG+si-FABP4 group,HG+si-FABP4+CCT020312 group.After 24 h,the expressions of FABP4 and PERK/eIF2α/ATF4/CHOP signaling pathway related proteins were detected.Results:Compared with Normal group,the level of FABP4 in the serum and pancreatic tissue of the GDM group were obviously up-regu-lated(P<0.05).FABP4 silencing obviously reduced FBG and IR,decreased the levels of blood lipids,CRP,TNF-α,IL-6 and MDA,and increased the levels of SOD and CAT(P<0.05).Furthermore,FABP4 silencing attenuated pancreatic and placental tissue damages.After CCT020312 up-regulated the phosphorylation levels of PERK and eIF2α and the protein expressions of ATF4 and CHOP,the inhibitory effects of FABP4 silencing on IR,inflammation,oxidative stress,and pancreatic and placental damages in GDM rats were reversed(P<0.05).FABP4 was up-regulated in HTR-8/SVneo cells induced by HG,and silencing FABP4 inhibited the protein ex-pression of the PERK/eIF2α/ATF4/CHOP pathway,while CCT020312 reversed this change(P<0.05).Conclusion:FABP4 silencing improves IR and ERS in GDM rats by inhibiting inflammation and oxidative stress,and the mechanism is related to the inhibition of PERK/eIF2α/ATF4/CHOP signaling pathway.
