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

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.Graphical abstractIn high glucose condition, SphK1/S1P2 signaling pathway was activated, which could induce the activation of the downstream transcriptional factor AP-1 and NF-κB, and then transfer into the nucleus to regulate the expression of fibrotic components (FN and TGF-β1) and inflammatory factors (ICAM-1 and iNOS). Thus, the progress of diabetic nephropathy was promoted. However, resveratrol could inhibit the activation of SphK1/S1P2 signaling pathway by via inhibition of AP-1 and NF-κB activation to reduce these above proteins expression and ameliorate mesangial cells proliferation and inflammation. Resveratrol could be a novel compound to relay the development of diabetic nephropathy.

Source: Journal of Functional Foods - February 18, 2019 Category: Nutrition Source Type: research