Effect of sitagliptin on tubulointerstitial Wnt/β‐catenin signalling in diabetic nephropathy

AIM: To investigate the effect of sitagliptin on Wnt/β-catenin signalling in the tubulointerstitium of diabetic nephropathy. METHODS: Forty male Wistar rats were divided into normal control (NC), diabetic model (DM), low and high-dose sitagliptin intervention groups (ST1 and ST2, respectively). Changes in the biochemical parameters and tubulointerstitial fibrosis index were observed. The levels of protein and gene expression of different indicators were detected via immunohistochemistry and real-time polymerase chain reaction. NRK-52E cells were divided into the normal control group, mannitol control group, high glucose group (HG), high glucose plus sitagliptin intervention group (HG + ST) and high glucose plus Wnt/β-catenin inhibitor group (HG + XAV939). The relevant indicators were examined by Western blot or enzyme-linked immunosorbent assay. RESULTS: Compared with the NC group, the blood glucose, glycosylated haemoglobin, 24 h urinary albumin, creatinine clearance and tubulointerstitial fibrosis index were significantly increased in the DM group. These parameters were decreased in the ST1 and ST2 groups compared to the DM group. Compared with the NC group, the levels of Wnt4, β-catenin, dipeptidyl peptidase-4 and α-smooth muscle actin were higher and E-cadherin was lower in the DM group. Sitagliptin treatment reversed these changes. In the high glucose-stimulated NRK-52E cells, sitagliptin and XAV939 inhibited the elevated expression of Wnt4, β-catenin, dipeptidyl peptidase-4, α-smooth muscle actin, transforming growth factor-β and fibronectin and restored E-cadherin activity. CONCLUSION: Sitagliptin may inhibit the tubulointerstitial Wnt/β-catenin signalling pathway in diabetic nephropathy and provide renal protection by alleviatinge renal tubulointerstitial transdifferentiation and fibrosis.