S1P Protects Against High Glucose-induced Vascular Endothelial Cell Injury Through S1PR1
Objective To explore the protective effect of sphingosine-1-phosphate(S1P)against high glucose-induced vascu-lar endothelial cell injury,and its mechanism.Methods Human umbilical vein endothelial cell(HUVEC)injury was induced by high glucose,and the cells were treated with S1P and small interfering RNA(siRNA)of S1PR1.S1PR1 transcription level was detected by qRT-PCR to screen si-S1PR1 with high silencing efficiency for subsequent experiments.Then the cells were divided into control group(NG),hypertonic group(L-Glu),high glucose group(HG),high glucose+S1P group(HG+S1P),high glu-cose+si-NC+S1P group(HG+si-NC+S1P),high glucose+si-S1PR1+S1P group(HG+si-S1PR1+S1P).CCK-8 assay was used to detect the viability of endothelial cells.Then cell migration ability was detected by scratch method,and tube-forming ex-periment was conducted to detect the angiogenesis ability of endothelial cells.The protein expression levels of S1PR1 and vascu-lar function-related molecules(VEGF,VE-cadherin and eNOS)were detected by Western blotting.Results Compared with con-trol group,the viability,migration and angiogenesis ability of endothelial cells in the high glucose group were significantly de-creased,while S1PR1 expression was reduced(all P＜0.01).Meanwhile,the expression levels of vascular function-related mole-cules(VEGF,VE-cadherin and eNOS)were significantly downregulated(all P＜0.01).After S1P treatment,S1PR1 expression and the viability,migration and angiogenesis ability of endothelial cells were significantly increased,and the protein expression levels of VEGF,VE-cadherin and eNOS were also increased significantly(P＜0.01).Downregulation of S1PR1 by si-S1PR1 a-bolished the restoring effects of S1P on the viability,migration,angiogenesis ability of endothelial cells and the functionally re-lated proteins(P＜0.01).Conclusion S1P plays a protective role against high glucose induced injury of endothelial cells by up-regulating VEGF,VE-cadherin and eNOS through S1 PR1.
sphingosine-1-phosphatehigh glucosevascular endothelial cellvascular function
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