Influence of fasudil on the epithelial-mesenchymal transdifferentiation of renal tubular epithelial cells in diabetic rats / 中华肾脏病杂志

ABSTRACT

Objective To investigate the influence of fasudil on the epithelialmesenchymal transdifferentiation of renal tubular epithelial cells in diabetic rats and to explore the mechanism. Methods Wistar mts were randomly divided into three groupscontrol,diabetes and fasudil-treatment.All the rots were sacrificed after three months of feeding with or without fasudil.Pathological changes of the glomeruli and renal interstitium were studied by periodic acidSchiff'S staining and Masson staining,respectively.Expression of ROCKI,α-SMA,E-cadherin and the distribution of β-catenin was examined by immunohistochemistry.Changes in the MYPT1 phosphorylation profile and α-SMA,E-cadherin and membrane β-catenin expression were detected bv Western blot.Changes in the levels of ROCKI,E-cadherin and total β-eatenin mRNA expression were analyzed by real-time PCR. Results Fasudil treatment notably attenuated renal interstitial fibrosis in diabetic rats.Compared to the control rats.diabetic rats showed an elevated phosphorylation of MYFF1(P<0.01),increased expression of α-SMA(P<0.01),decreased expression of E-cadherin and membrane β-catenin(P<0.01,respectively)and increased expression of ROCKI,total β-catenin mRNA(P<0.01,respectively),decreased expression of E-cadherin mRNA(P<0.01 ). Fasudil treatment for diabetic rats attenuated MYPT1 phosphorylation (P<0.01), decreased α-SMA expression (P<0.01), increased E-cadherin and membrane (β-catenin expression (P<0.01, respectively), and reduced ROCKI, total β-catenin mRNA expression (P <0.01, respectively), increased expression of E-cadherin mRNA (P<0.01). Conclusions Fasudil may reduce the epithelial-mesenchymal transdifferentiation and renal interstitial fibrosis in diabetic rats through the inhibition of ROCK activity. Such effect further facilitates the recovery of the cell-cell adhesion among renal tubular epithelial cells and the formation of adhesion complex.