The influence of fasudil on the epithelial-mesenchymal transdifferentiation of renal tubular epithelial cells from diabetic rats - 17/02/10
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Abstract |
To investigate the influence of fasudil on the epithelial-mesenchymal transdifferentiation of renal tubular epithelial cells from diabetic rats and explore the mechanisms of this effect. Wistar rats were randomly divided into the following three groups: control, diabetes and fasudil-treatment. All rats were sacrificed after three months of feeding with or without fasudil treatment. Pathological changes to the glomeruli and renal interstitium were studied using Periodic acid-Schiff’s staining and Masson staining, respectively. Expression of ROCK1, ⍺-SMA, E-cadherin and the distribution of β-catenin in rat renal cortex were revealed by immunohistochemistry. Changes in the MYPT1 phosphorylation profile and ⍺-SMA, E-cadherin and membrane β-catenin expression were revealed by western blot. Changes in the levels of ROCK1, E-cadherin and total β-catenin mRNA expression were analyzed by real-time PCR. Fasudil treatment notably attenuates renal interstitial fibrosis in diabetic rats. Compared to the control rats, diabetic rats showed elevated phosphorylation of MYPT1, increased expression of ROCK1 and ⍺-SMA, decreased expression of E-cadherin and membrane β-catenin, and increased expression of ROCK1 and total β-catenin mRNA, decreased expression of E-cadherin mRNA. Fasudil treatment of diabetic rats resulted in attenuated MYPT1 phosphorylation, decreased ROCK1 and ⍺-SMA expression, increased E-cadherin and membrane β-catenin expression, and reduced ROCK1 and total β-catenin mRNA expression, increased expression of E-cadherin mRNA. In conclusion, fasudil may reduce the epithelial-mesenchymal transdifferentiation and renal interstitial fibrosis in diabetic rats through a mechanism by which ROCK activity is inhibited, which further facilitates the recovery of the cell-cell adhesions among renal tubular epithelial cells and adhesion complex formation.
Le texte complet de cet article est disponible en PDF.Keywords : Diabetic nephropathy, Fasudil, Epithelial-mesenchymal transdifferentiation of renal tubular epithelial cells
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Vol 64 - N° 2
P. 124-129 - février 2010 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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