Rosiglitazone Blocked Tubular Epithelial To Mesenchymal Transtion (EMT) Induced By TGF-β1

Objective: Peroxisome proliferators activated receptorγ, (PPARγ) agonists are increasingly used in patients with diabetes, and small studies have suggested a beneficial effect on renal function, but their effects on renal fibrosis are unknown. The aims of this study were to investigate the effects of the PPARγagonist rosiglitazone on human proximal tubular epithelial cell activation.Methods: TGF-β1 treated human proximal tubular epithelial cells were cultured with or without rosiglitazone at different concentrations. The HKC EMT was assessed by expression ofα-smooth muscle actin (α-SMA), and deposition of fibronectin (FN) by western blotting. MMP-2 were measured in equal volumes of supernatant using gelatin zymography. Immunofluorescence was used to detectα-SMA and FN expression in cultured HKC.Results: TGF-β1 stimulated FN andα-SMA expression in HKC in time-course, while rosiglitazone abrogated this effect in a dose-dependent way, which is similar to GW1929. RGZ could decrease FN expression in HKC alone. TGF-β1 increased MMP-2 expression in supernatant of HKC in time-course, which could not be inhibited by RGZ.Conclusion: Rosiglitazone could abolishα-SMA expression induced by TGF-β1 in HKC in a dose-dependent way. Meanwhile, we found that rosiglitazone could block TGF-β1-induced FN deposition and its extracellular assembly in HKC. These suggested that the effects of RGZ on delaying progression of CRF might associate with this action. Objective: To investigate the mechanism of rosilitazone in treating chronic renal dieases.Methods: The animal model of renal disease was induced by unilateral ureteral obstruction (UUO) in male CD-lmice. The mice were divided into three groups: the sham, UUO, and UUO receiving rosiglitazone treatment daily. The de novo expression ofα- smooth muscle actin (α-SMA) and fibronectin (FN) in tissues were assessed by Western blotting. Hematoxylin—Eosin staining was used to observed morphology of obstructed kidney. Immunofluorescence was used to detect FN andα-SMA expression in kidney.Results: The de novo expression ofα-SMA and increased expression of FN were observed in UUO mice in time-course. And rosiglitazone could attenuate this effect and improve renal tissue injury.Conclusion: Rosiglitazone is a drug for amelioration of renal fibrosis in mouse UUO model. Objective: To investigate the relationship between high-glucose-induced fibronectin(FN) expression and up-regulation of integrin-linked kinase in human kidney tubular epithelial cells(HKC).Methods: Cultured human kidney tubular epithelial cells and streptozotocin (STZ)-induced diabetic model of CD-1 mice were studied. We used western blotting to detect the expression of FN and ILK. The kinase dead ILK plasmid (pCMV-kdILK) were transferred to HKC. The blockage of ILK activation on the action of high-glucose on HKC were studied.Results: Four weeks after injection of STZ, CD-1 mice had a higher blood glucose level than control (20.3±2.7 vs 6.1±1.4 mmol/L). Meanwhile, diabetic mice expressed more fibronetin and integrin-linked kinase than control; and statistical analysis indicated there was a close relationship between the expression of FN and ILK. High-glucose could up regulate FN and ILK expression in cultured HKC in time course. Blockage of ILK activation by pCMV-kdILK abrogated high-glucose-incuced FN expression in HKC.Conclusion: High-glucose could induce FN expression through up regulating ILK expression. Blockage of ILK activation abrogated this effect. This indicated a close relationship between the expression of FN and ILK in HKC.