Selective deletion of the endothelial sphingosine-1-phosphate 1 receptor exacerbates kidney ischemia–reperfusion injury

摘要: The role for the endothelial sphingosine-1-phosphate 1 receptor (S1P R) in acute kidney injury (AKI) remains unclear as germline S1P1R deletion is embryonically lethal. Here, we generated conditional deficiency by crossing mice with floxed expressing a tamoxifen-inducible form of Cre recombinase under transcriptional control platelet-derived growth factor-β ( Pdgfβ ) gene. Mice tamoxifen-induced had increased renal tubular necrosis, inflammation, and impaired vascular permeability, well exacerbated apoptosis after ischemic AKI compared tamoxifen-treated wild-type mice. Moreover, resulted hepatic AKI. As potential mechanism injury, S1P1R–null markedly reduced HSP27 expression Cultured glomerular cells treated specific antagonist (W146) 3 days also showed vehicle-treated cells. Finally, W146 Thus, our studies demonstrate protective against most likely regulating barrier integrity expression.