Effects of the S1P/S1PR1 signaling pathway on high glucose-induced NRK-52E epithelial- mesenchymal transdifferentiation via regulation of ROS/NLRP3

Diabetic nephropathy (DN) ranks as the predominant complication among diabetics, culminating in renal fibrosis. A variety of processes play a role in its pathophysiology, with the epithelial-mesenchymal transition (EMT) in renal tubular cells being intimately linked to renal fibrosis. Sphingosine 1-phosphate (S1P) functions via G protein-coupled receptors and is involved in multiple signal transmission pathways. Research has demonstrated that the S1P/S1PR pathway controls fibrosis and inflammation. However, the interaction between S1P/S1PR and the pathophysiology of EMT remains ambiguous. The objective of this research was to explore the function of the S1P/S1PR pathway in EMT triggered by high glucose (HG) and how it operates. Employing varied glucose levels for cell treatment, we discovered that HG markedly increased the S1P and EMT marker levels in renal tubular epithelial cells. In vitro, inhibition of S1P1 by FTY720 resulted in a marked decrease in renal tissue EMT. Activation of oxidative stress (OS) can lead to diabetes, with the NLRP3 inflammasome contributing to the inflammation linked to diabetes. Research indicates that blocking reactive oxygen species (ROS) can prevent the NLRP3 inflammasome produced. This investigation examined S1P expression, revealing that blocking S1PR1 led to a reduction in both ROS and NLRP3 inflammasome metrics, it indicates the role of S1P in initiating and advancing HG-induced EMT. The combination of S1P/S1PR1 suppresses HG-induced EMT through the modulation of the ROS/NLRP3 pathway.