Hyperglycemia Promotes Pyroptosis By Upregulation Of Yap1 To Induce Impaired Trophoblast Cell Development In Hypertensive Preeclampsia During Pregnancy

Objective: Preeclampsia(PE)is a serious hypertensive disease in pregnancy,which seriously endangers the health of mother and child.Its main pathogenesis is impaired trophoblast cell development.Although diabetes is a high risk factor for PE,the current mechanism is not clear.Trophoblast pyroptosis plays a key role in the pathogenesis of PE and diabetes can promote it.Yap1 regulates cell growth and proliferation and is an important mediator of inflammatory response.Therefore,this article proposed "high blood glucose by raising Yap1 promote cell focal late pregnancy induced hypertension,preeclampsia nourish cells damaged" hypothesis,proposed on the basis of in vitro cultivation of sertoli cell,study the effect of hyperglycemia on sertoli cell function and its effect on the potential molecular mechanisms,as high blood sugar of PE and other pregnancy induced hypertension disease provide new targets for intervention.Methods: Migration and wound healing analysis was designed to measure the role of HG(25 m M)in trophoblast cell migration and invasion.Western blot was used to detect the expression of NLRP3,caspase1 and IL-1β.The ROS probe is used to detect the ROS level after HG treatment.Mito-Tracker green was used to observe mitochondrial morphology.Western blot and q TR-PCR were used to detect the expression of Yes-related protein 1(Yap1).The statistical analysis of all data was expressed as mean±standard deviation(±SD).Graphpad Prism5.0.1 was used to analyze and plot the data.A 95% confidence interval was selected,and P<0.05 indicated that the difference was significant.Results: The results showed that HG inhibited migration and invasion ability and promoted the expression of pyrolysis and pyroptosis-related proteins NLRP3,caspase1,IL-1β and GSDMD.We also observed abnormal mitochondrial morphology and function after HG treatment.After HG treatment,protein and m RNA levels of Yap1 also increased.Small interfering RNA was used to suppress Yapl expression,and its reduced apoptosis and mitochondrial function were observed.Conclusions:(1)High glucose upregulates the expression level of YAP1 in HTR8-S/Vneo cells;(2)High glucose promotes pyrolysis of HTR8-S/Vneo cells;(3)High glucose promotes pyrolysis of HTR8-S/Vneo cells by up-regulating YAP1.