ETS proto-oncogene 1 modulates PTP1B expression to participate in high glucose-mediated endothelial inflammation  

作　　者：Lili Jiang Jincai Liang Tianhai Wang Fufen Meng Wenming Duan 

机构地区：[1]Department of Anesthesiology,the Third Hospital,Affiliated to the Xinjiang Medical University,Urumqi 830011,China [2]Department of Anesthesiology,the Fourth People′s Hospital of Qinghai Province,Xining 810000,China [3]Department of Anesthesiology,Chengdu BOE Hospital,Chengdu 611743,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第4期565-573,共9页生物化学与生物物理学报（英文版）

基　　金：the grant from the Initiating Fund of the Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2019D01C257)。

摘　　要：Hyperglycemia-induced endothelial inflammation participates in the pathogenesis of cardiovascular complications in diabetics.Previous studies showed that protein tyrosine phosphatase 1B(PTP1B)and ETS proto-oncogene 1(ets1)are involved in hyperglycemia-induced endothelial inflammation.In this study,we hypothesized that ets1 modulates PTP1B expression,thus playing a crucial role in hyperglycemia-induced vascular endothelial inflammation.Our results indicated that high glucose increases monocyte/endothelial adhesion,vascular cell adhesion molecule-1(VCAM-1)expression and p65 phosphorylation in human umbilical vein endothelial cells(HUVECs).Moreover,high glucose-mediated endothelial inflammation is reversed by PTP1B silencing.In addition,high glucose increases ets1 expression in HUVECs.Ets1 silencing reverses high glucose-mediated endothelial inflammation.Furthermore,the effect of ets1 overexpression is similar to that of high glucose treatment,which is counteracted by si-PTP1B.The results from ChIP assays indicated that ets1 occupies the PTP1B promoter region.Ets1 overexpression enhances PTP1B promoter activity,which is disappeared after specific binding site mutation.In vivo experiments demonstrated that the expressions of VCAM-1,PTP1B,and ets1,as well as the phosphorylation of p65 are augmented in the aorta of diabetic rats.In conclusion,ets1 contributes to hyperglycemia-mediated endothelial inflammation via upregulation of PTP1B expression.

关 键 词：ENDOTHELIAL ETS1 high glucose INFLAMMATION PTP1B 

分 类 号：R730.2[医药卫生—肿瘤]