1,25(OH)2D3 is Involved in the Regulation of Caspase-3/GSDME Pathway-Mediated Cellular Pyroptosis on Kidneys of Rats with Diabetic Nephropathy.

Abstract

This study sought to investigate the presence of caspase-3/Gasdermin E (GSDME) pathway-induced cellular pyroptosis in diabetic nephropathy (DN), and to clarify the mode of action of this pathway and the regulatory role of 1,25(OH)2D3. A rat model of DN was constructed using Streptozotocin (STZ) in combination with a high-fat, high-sugar diet. The results show that 1,25(OH)2D3 reduces pyroptosis, protects kidney tissues, reduces renal cells damage, and decreases serum creatinine, blood urea nitrogen, and 24-hour urine protein (24hUpro) in rats with DN. Pathological changes such as glomerular mesangial stroma, glomerular basement membrane thickening, tubular vacuolar degeneration, and interstitial fibrosis in the kidney tissue of rats with DN were significantly ameliorated by the intervention of 1,25(OH)2D3. In addition, 1,25(OH)2D3 down-regulated the activation of the inflammatory factor NF-κB, down-regulation of caspase-8 expression and inhibition of protein expression of DN rat focal death-associated protein cleavage caspase-3, GSDME and GSDME-N. These findings support the protective effect of 1,25(OH)2D3 on kidney tissues of rats with diabetic nephropathy may be related to the inhibition of the caspase-3/GSDME pathway in the presence of pyroptosis.