A Study On Pathological Process Of Preeclampsia Proteinuria Via HMGB1-Caveolin-1 Pathway

ObjectiveTo offer new research thought on the pathogeny and prevention in preeclampsia,this study explored whether severe preeclampsia serum can induce high molecular weight protein(HMWP)hyperpermeability and the overexpression of Caveolin-1(CAV-1)in Glomerular Vascular Endothelial Cells(GVEC)via HMGB1-CAV-1 pathway.MethodsCultured primary human GVEC,and tested the dynamic permeability of GVEC to HMWP by Transwell chamber.Detected the expression of CAV-1 by Immunofluorescence and Western blot for quantitative analysis.Detected the expression of HMGB1 in severe preeclampsia and normal pregnancies placenta by Immunohistochemistry and Western blot,and measured the serum level of HMGB1 in severe preeclampsia and normal patients by ELISA.Transwell chamber was also used to test the dynamic permeability of GVEC to HMWP,when treated with HMGB1 inhibitor--Glycyrrhizic acid(GA)and recombinant HMGB1.The CAV-1 expression of GVEC on above-mentioned condition was detected by Western blot.ResultsSevere preeclampsia serum promoted GVEC hyperpermeability by enhancing CAV-1 expression.The CAV-1 expression decreased when dealt with CAV-1 inhibitor Methyl beta cyclodextrinthe.The HMGB1 expression on severe preeclampsia placenta was significant higher than normal pregnancies placenta.HMGB1 mainly located in placental syncytiotrophoblast.Compared with normal pregnancies serum,the HMGB1 of severe preeclampsia serum was on a higher level.Severe preeclampsia serum could induce the CAV-1 expression and HMWP permeatibility,however,it could be inhibited by pretreated GA.Human recombinant HMGB1 induced the CAV-1 expression and HMWP permeability of GVEC,which was suppressed by GA.ConclusionsTrophoblast cells on severe preeclampsia placenta may release HMGB1 into serum,enhance the expression of CAV-1,induce the HMWP hyperpermeability of GVEC,and result in proteinuria...