Resveratrol inhibits high glucose-induced activation of AP-1 and NF-κB via SphK1/S1P2 pathway to attenuate mesangial cells proliferation and inflammation

Diabetes nephropathy (DN) is the most common microvascular complications of diabetes, as hyperglycemia induces mesangial cell (MC) proliferation and inflammation and subsequently contributes to the development of renal fibrosis. Sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate receptor 2 (S1P2) signaling pathway could activate AP-1 and NF-κB, which played a key regulatory role in the pathological progression of DN. This study investigates whether resveratrol (RSV) plays a regulatory role by SphK1/S1P2 pathway in MCs proliferation and inflammation under high glucose condition. Herein, we found that RSV inhibited MCs proliferation and attenuated high glucose (HG)-induced FN, TGF-β1, ICAM-1, iNOS, SphK1 and S1P2 expression and inhibited SphK1 activity andS1P production, which was also in accordance with MCs transfected with wild-type SphK1WT plasmid. Furthermore, RSV remarkably reduced AP-1 and NF-κB activation. Overall, these results indicated that RSV could be a potential and valuable resource of natural compounds for DN treatment via SphK1/S1P2 pathway.