Study On Role Of MiR-137 In Regulating Vascular Endothelial Cells And Trophoblast Cells In Gestational Diabetes Mellitus

Objective: To explore the expression profiles of microRNA(miR)-137 in gestational diabetes mellitus(GDM)and normal pregnant women,and how miR-137 regulates biological functions of vascular endothelial cells(VECs)and trophoblast cells,and analyze the underlying molecular mechanisms of pathological changes and disease progression in GDM.Methods: Placental biospies and peripheral blood of normal pregnant and GDM women were collected,and level of miR-137 was detected in placental biospies and peripheral plasma;We measured expression of miR-137 in high glucose(HG)treated trophoblast cells(HTR-8/SVneo)and human umbilical vein endothelial cells(HUVECs).The miR-137 overexpressed HUVECs and HTR-8/SVneo were achieved,and we measured level of chemokine(C-C motif)ligand 2(CCL2),interleukin(IL)-6,IL-8 and vascular endothelial growth factor(VEGF)in supernatants of HUVECs,and we detected recruitment and adhesion ability to monocytes,viability,tube formation ability and expression of activation molecules in HUVECs.Level of FNDC5 was determined in placenta biospies and HG-exposed HTR-8/SVneo cells,and we tested the regulation of miR-137 on FNDC5.Plasmid vectors were used to infect HTR-8/SVneo cells and promote expression of FNDC5,and viability along with migration ability of these cells were analyzed.Level of AMP-activated,alpha 1 catalytic subunit(AMPKɑ1)was measured in placenta biospies and HG-treated HTR-8/SVneo cells,withproduction of IL-6 being analyzed in HG-exposed HTR-8/SVneo cells.The regulation of miR-137 on AMPKɑ1 and IL-6,role of agonist and inhibitor of AMPKɑ1 in regulating secretion were all determined in HTR-8/SVneo cells.Lastly,we detected the influence of HG,miR-137,IL-6,agonist and inhibitor of AMPKɑ1 on viability and proliferation of HTR-8/SVneo cells.Results: Comparing to normal pregnant women,level of miR-137 augmented in placenta tissues of severe-GDM women and peripheral plasma of GDM women.HG treatment upregulated expression of miR-137 in HUVECs;Level of CCL2 and IL-6 elevated and expression of IL-8 and VEGF decreased in supernatants of miR-137 overexpressed HUVECs;High level of miR-137 in HUVECs promoted expression of activation markers,and enhanced monocytes migrating and adhering to HUVECs,and the viability and tube formation ability of HUVECs were suppressed.Expression of FNDC5 dampened in placenta tissues of GDM women;HG treatment promoted expression of miR-137 and restricted level of FNDC5 in HTR-8/SVneo cells;Overexpressing miR-137 in HTR-8/SVneo cells downregulated level of FNDC5 and suppressed viability and migration ability of the cells;Upregulating level of FNDC5 in miR-137 overexpressed HTR-8/SVneo cells promoted the viability and migration ability of cells.Level of AMPKɑ1 decreased in placenta tissues of GDM women and HG-exposed as well as miR-137 overexpressed HTR-8/SVneo cells;HG treatment and high level of miR-137 and inhibitor of AMPKɑ1all promoted production of IL-6 and restricted viability and proliferation of HTR-8/SVneo cells.Conclusion: On the one hand,high level of miR-137 in GDM women contributes to dysfunction of HUVECs in HG condition,on the other hand,high level of miR-137 suppresses viability and migration of HTR-8/SVneo cells via downregulating FNDC5,and HG restricts viability andproliferation of HTR-8/SVneo cells through miR-137/AMPKɑ1/IL-6 axis,all probably playing a role in accelerating pathological changes and progression of GDM.