Abstract: Objective To explore the potential mechanism by which canagliflozin alleviateskidney injury in streptozotocin ( STZ ) -induced diabetic nephropathy mice through TGF-β /STAT3. Methods A diabetic nephropathy mouse model was established using STZ. Mice were divided into 5 groups: control group, STZ-induced diabetic nephropathy mice group, canagliflozintreated group, TGF-β inhibitor-treated group, and STAT3 inhibitor-treated group. Renal weight / body weight ratio, urinary albumin, renal function parameters, serum TGF-β level and the phosphorylation level of STAT3 in the kidney tissues were measured. Results Mice with diabetic nephropathy exhibited signs of renal injury, including a significant increase in renal weight / bodyweight ratio and urinary albumin (P < 0. 05), whereas these indices returned to normal levels aftercanagliflozin treatment. The serum TGF-β level and phosphorylation level of STAT3 in tissues wereelevated in diabetic nephropathy mice (P < 0. 05), while they returned to similar levels as that inthe control after canagliflozin treatment. In addition, the TGF-β expression level was positively correlated with the STAT3 phosphorylation level (P < 0. 05). Conclusion Canagliflozin attenuated renal injury in diabetic nephropathy by modulating TGF-β and STAT3 pathways.

Key words: canagliflozin, TGF-β, STAT3, diabetic nephropathy, kidney injury