Xiaojun Ren1,2, Ruifang Zhu3, Gaohong Liu4, Fuping Xue5, Yanhong Wang6, Jia Xu2, Wan Zhang2, Weimin Yu2, Rongshan Li4. 1. Department of Nephrology, Postdoctoral Workstation of Shanxi Medical University Second Affiliated Hospital, Taiyuan, China. 2. Department of Nephrology, Shanxi Dayi Hospital (Shanxi Academy of Medical Sciences), Taiyuan, China. 3. School of Nursing, Shanxi Medical University, Taiyuan, China. 4. Department of Nephrology, The Affiliated People's Hospital of Shanxi Medical University, Shanxi Provincial People's Hospital, Taiyuan, China. 5. Department of Nephrology, Shanxi Provincial Corps Hospital of Chinese People Armed Police Forces, Taiyuan, China. 6. Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, China.
Abstract
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.
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.
Authors: Sheng-Yao Cheng; Alexander T H Wu; Gaber El-Saber Batiha; Ching-Liang Ho; Jih-Chin Lee; Halimat Yusuf Lukman; Mohammed Alorabi; Abdullah N AlRasheedi; Jia-Hong Chen Journal: Biology (Basel) Date: 2022-02-17
Authors: Eslam E Abd El-Fattah; Sameh Saber; Mahmoud E Youssef; Hanan Eissa; Eman El-Ahwany; Noha A Amin; Mohammed Alqarni; Gaber El-Saber Batiha; Ahmad J Obaidullah; Mohamed M Y Kaddah; Ahmed Gaafar Ahmed Gaafar; Ahmed A E Mourad; Gomaa Mostafa-Hedeab; Amir Mohamed Abdelhamid Journal: Front Pharmacol Date: 2022-01-12 Impact factor: 5.810