The Activation of Peroxisome Proliferator-activated ReceptorγEnhances Insulin Signaling Pathways Via Up-regulating Chemerin Expression in High Glucose Treated HTR-8/SVneo Cells  

作　　者：Zhou Xuan Wei Li-Jie Li Jia-Qi Zhang Jing-Yi Zhu Sheng-Lan Zhang Hui-Ting Jia Jing Yu Jun Wang Shao-Shuai Feng Ling 

机构地区：[1]Department of Obstetrics and Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

出　　处：《Maternal-Fetal Medicine》2020年第3期131-140,共10页母胎医学杂志（英文）

基　　金：This study was supported by the National Key R&D Program of China(No.2016YFC1000405 and No.2018YFC1002903)

摘　　要：Objective:To investigate whether peroxisome proliferator-activated receptorγ(PPARγ)agonists,rosiglitazone and GW1929,activate the phosphatidylinositol 3-kinase(PI3K)-AKT/protein kinase B pathway and the mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase1/2(ERK1/2)pathway by upgrading the expression of chemerin.Methods:The HTR-8/SVneo trophoblastic cells were cultured in vitro in high glucose concentration(25 mmol/L)to mimic gestational diabetic phenotypes.We transfected small interfering RNA into HTR-8/SVneo cells to silence two receptors of chemerin,that are chemokine-like receptor 1(CMKLR1)and G protein-coupled receptor1(GPR1).And recombinant human chemerin,PPARγagonists(rosiglitazone,10μmol/L and GW1929,10μmol/L)and PPARγinhibitor(GW9662,5μmol/L)were additionally added to the medium,respectively.The existence of chemerin was verified by immunocytochemistry,and the expressions of PPARγ,chemerin,and its receptors as well as insulin signaling-related factors PI3K,AKT2,and MAPK(ERK1/2)were detected by real time quantitative-polymerase chain reaction and western blot.Results:Chemerin existed in the HTR-8/SVneo cells.Effects of chemerin on PI3K-AKT pathway and MAPK(ERK1/2)pathway were dependent on the density of chemerin.When rosiglitazone and GW1929 were added to the medium,the mRNA levels of PI3K,AKT2,and MAPK1 were upregulated(P<0.05).Conversely,GW9662 downregulated the mRNA levels of AKT2 and MAPK1(P<0.05).Rosiglitazone and GW1929 increased the protein levels of PPARγ,chemerin,CMKLR1 and GPR1(P<0.05).Rosiglitazone and GW1929 had no effect on the expression of PI3K p110βand phospho-AKT2 without CMKLR1(P>0.05).Meanwhile,the expression of phospho-ERK2 remained unaffected in the absence of GPR1(P>0.05).Conclusion:Both rosiglitazone and GW1929 have the effect of improving insulin signaling pathways via upgrading the level of chemerin in high glucose treated HTR-8/SVneo cells.

关 键 词：GLUCOSE CHEMERIN Chemokine-like receptor 1 G protein-coupled receptor 1 GW1929 Phosphatidylinositol 3-kinase PPAR gamma Protein kinase B beta p42 MAPK ROSIGLITAZONE 

分 类 号：R714.256[医药卫生—妇产科学]