The role of TGF-β/Smad pathway in podocyte epithelial-mesenchymal transition in diabetic nephropathy

Objective: Diabetic nephropathy (DN) is a common microvascular complication of Diabetes Mellitus. Podocyte damage associated with epithelial mesenchymal transition (EMT) can cause DN. It was aimed to investigate the potential roles of urinary levels of TGF-β/Smad pathway-related proteins, which are involved in the podocyte EMT, as an early biomarker in the diagnosis of DN in this study. Methods: 60 patients diagnosed with Type 2 Diabetes Mellitus (T2DM) and 20 healthy volunteers were included in the study. The patients were divided into three groups according to their albuminuria levels. Creatinine, glucose and hemoglobin A1c (HbA1c) were measured in blood samples, albumin and creatinine levels were measured in urine samples. The estimated Glomerular Filtration Rate (eGFR) was calculated. Nephrin, podocin, podocalyxin, podoplanin, smad2, smad7 and TGF-β1 in urine were analyzed by ELISA. The results were evaluated with urine creatinine ratio. Sensitivity and specificity of these markers for the diagnosis of DN were calculated by Receiver Operating Characteristic (ROC) analyses. Results: Urine nephrin, podocin, podocalyxin, podoplanin, TGF-β1, smad2 and smad7 levels were significantly higher in the micro and macroalbuminuric T2DM groups compared to the control group. All of these proteins were negatively correlated with eGFR and positively correlated with diabetes duration, HbA1c, and urinary albumin creatinine ratio. It was observed that both sensitivity and specificity of podocin, nephrine and smad2 were higher than microalbuminuria in the diagnosis of DN. Conclusion: This study shows that TGF-β/Smad signaling pathway-related proteins are increased during podocyte EMT in DN and their superiority over microalbuminuria in terms of sensitivity and specificity in the diagnosis of DN.