Leptin And Transforming Growth Factor-B₁ Mediate Tubular Epithelial-Mesenchymal Transition In Type 2 Diabetic Rats

Objective:To explore the association and role of leptin and transforming factor-β₁ on tubular epithelial-mesenchymal transition(EMT) in induced type 2 diabetic rats.Methods:Eight weeks old Wistar rats(n=37) were divided into two groups:model(n=25)and control groups(n=12).The model group rats were intraperitoneally injected low-dose streptozotocin(STZ,30mg/kg)after having the sucrose-and fat-enriched diets for eight weeks.The control group rats were given common diet.Blood glucose,HbA1c,cholesterol, triglyceride,BUN,Scr,serum leptin,insulin and 24-hour urinary protein excretion were detected at 0,8,9,12 and 16 weeks respectively.Six rats were sacrificed at 9 weeks in every group.The others were sacrificed at 16 weeks.Kidney index of rats were measured. HE staining were used to observe the renal pathological changes.Protein expressions of OB-R,TGF-β₁andα-smooth muscle actin(α-SMA) were assessed with immunocytochemistry.Results:Some pathological characteristics of diabetic nephropathy exist in type 2 diabetic rats.Blood glucose,HbA1c,cholesterol,triglyceride,BUN,Scr,leptin,insulin,24 - hour urinary protein,kidney index,protein expressions of TGF-β₁ andα-SMA were significantly increased in DM as compared with control(P＜0.05,P＜0.01).Protein expressions of TGF-β₁ andα-SMA exhibit a positive correlation with serum leptin (P＜0.01),whereas OB-R exhibit a negative correlation with serum leptin in DM (P＜0.01).In additions,we found that TGF-β₁,α-SMA and OB-R mainly located in renal tubules by immunohistochemical staining.Conclusions:Elevated serum leptin probably inhibits expressions of leptin receptor in kidney of type 2 diabetes.leptin and TGF-β₁ are possibly involved in the pathogenesis of EMT in diabetic nephropathy rats.