Hydrogen Sulfide Protects Human Umbilical Vein Endothelial Cells Against High Glucose-induced Injuries By Mediating Ihh/Gli1 Pathway

BackgroundChina has the largest number of diabetes patients in the world.Diabetes mellitus can lead to a variety of diabetes complications,such as stroke,coronary heart disease and so on,resulting in a decline in quality of life.The mechanism of diabetic vascular complications is very complicated.It is still a hot spot to explore the pathophysiology and inhibitory mechanisms of diabetes complications.The diabetic vascular complications result from the dysfunction of several vascular physiology components mainly involving the endothelium,vascular smooth muscle and platelets.Hyperglycemia induces the dysfunction of endothelial cells directly or indirectly.In the early states.the mechanisms of diabetes caused the damage in vein endothelial cells,researchers concentrated on polyol metabolic pathway,advanced glycationend-products(AGEs),protein kinase C(PKC)and so on.In recent years,more and more researchers gradually drew attention to multiple cell signal pathways to explore the mechanisms of diabetes caused the damage in vein endothelial cells.Hedgehog-Gli signaling pathway is mainly composed by signal pepfide(Hedgehog),transmembrane receptors(Ptch,Smo)and downstream transcription factor(Gli1,Gli2 and Gli3).Gli1 plays a role in transcriptional activation.Many studies shown that shown that Ihh/Gli1 signaling pathway plays vital role in differentiation,survival and proliferation of endothelial cells.Whether high glucose can inhibit the Ihh/Gli1 signaling pathway in vascular endothelial cells?Whether exogenous H2S can protect HUVECs against the HG-induced injuries by regulating Ihh/Gli1 pathways.It’s not clear.Hydrogen sulfide(H2S)was considered the third endogenous gaseous signal molecule,followed with NO and CO,which plays vital roles in biological effect.It have been proved that exogenous H2S can protect HUVECs against the HG-induced injuries by inhibiting p38 MAPK/necroptosis signal pathway and leptin/leptin receptor signal pathway.Whether exogenous H2S can protect HUVECs against the HG-induced injuries by regulating Ihh/Gli1 signal pathway?It’s not clear.In conclusion,our study focus on(1)the effect of high glucose on Ihh/Gli1 signaling pathway in human umbilical vein endothelial cells(HUVECs);(2)the role of Ihh/Gli1 pathways in HG-induced injuries in HUVECs;(3)whether exogenous H2S can protect HUVECs against the HG-induced injuries by regulating Ihh/Gli1 signal pathway,which may provide new evidence for further study of the mechanism of hyperglycemia-induced endothelial injury and the mechanism of H2S protecting HUVECs against hyperglycemia-induced endothelial injury.Research methods1.The HUVECs viability was examined by MTT assay.2.The Ihh and Gli1 expression levels were detected by western blot assay.3.Detection of the apoptosis rates was performed by Hoechst 33258 staining followed by photofluorography.Results1 High glucose down-regulated Ihh and Gli1 expression levels in HUVECs;2 The inhibitor of Ihh/Gli1 signaling pathway induced the decline of the expression of Ihh and Gli1 in HUVECs;3 The inhibitor of Ihh/Gli1 signaling pathway induced the decline of the viability of HUVECs;4 The inhibitor of Ihh/Gli1 signaling pathway induced apoptosis in HUVECs;5 The agonist of Ihh/Gli1 signaling pathway alleviated high glucose-induced the decline of the viability of HUVECs;6 The agonist of Ihh/Gli1 signaling pathway reduced high glucose-induced apoptosis of HU VECs;7 The agonist of Ihh/Gli1 signaling pathway attenuated high glucose-induced decline of the expression of Ihh and Gli 1 in HUVECs;8 Exogenous H2S attenuated high glucose-induced decline of the expression of Ihh and Gli1 in HUVECs;9 Exogenous H2S reduced high glucose-induced the decline of the viability of HUVECs;10.Exogenous H2S reduced high glucose-induced apoptosis of HUVECs.Conclusion1 High glucose induced endothelial injuries by inhibiting Ihh/Gli1 signaling pathway.2 Exogenous H2S protected HUVECs against high glucose-induced injuries by mediating Ihh/Gli1 pathway.