Effects of Dapagliflozin on Renal Interstitial Fibrosis in Diabetic Rats through Smad3, TIMP1 and MMP24 Pathway

Abstract

This research was designed to probe into the effects of Dapagliflozin on renal interstitial fibrosis in diabetic rats through Smad3, TIMP1 and MMP24 pathway. Methods: Rats were bought to establish models, and then intervened by Dapagliflozin. Human mesangial cell lines (HMCs) stimulated by high glucose were purchased, and the Smad3, TIMP1 and MMP24levels in rats after modeling and Dapagliflozin intervention were detected. The Smad3, TIMP1 and MMP24 protein expressionin kidney tissue was examined after the rats were killed, and the expression in an intervention group (IG) and a blank group (BG) were analyzed. The cells were divided into three groups: Dapagliflozin intervention (Group 1), TGF-β1/Smad3 pathway inhibitor SIS3 intervention (Group 2) and no intervention (Group 3). The TIMP1 and MMP24 levels were assessed. Results: The Smad3 and MMP24 levels in group A were higher than those in other two groups (p<0.05), while those of TIMP1 were lower (p < 0.05). Compared with pre-intervention, the Smad3 and MMP24 levels in groups A and B decreased (p < 0.05), while those of TIMP1 increased (p < 0.05). The Smad3 and MMP24 protein levels in groups A and B were higher than those in other two groups (p < 0.05), while those of TIMP1 was lower (p < 0.05). Compared with the BG, the Smad3 and MMP24 expression in the IG was lower (p < 0.05) and that of TIMP1 was higher (p < 0.05). The TIMP1 expression in Group 3 was lower (p < 0.05) and that of MMP24 was higher than those in Groups 1 and 2 (p < 0.05). Conclusion: Dapagliflozin can treat diabetic renal interstitial fibrosis by inhibiting TGF-β1/Smad3 signaling pathway, decreasing MMP24 and increasing TIMP1.