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Tranilast attenuates TGF-beta1-induced epithelial-mesenchymal transition in the NRK-52E cells
Pakistan Journal of Pharmaceutical Sciences. 2014; 27 (1): 51-55
in English | IMEMR | ID: emr-142979
ABSTRACT
We previously reported that tranilast can halt the pathogenesis of chronic cyclosporine nephrotoxicity in rats via the transforming growth factor-beta [TGF-beta] /Smad pathway, an important signaling system involved in epithelialmesenchymal transition [EMT], but the exact underlying cellular mechanisms are not yet clear. Thus, by selecting [0]TGF-beta1-induced normal rat kidney proximal tubular epithelial cells [NRK-52E] as a model, we demonstrated potential modifying effect of tranilast on EMT-induced by TGF-beta1 in vitro. NRK-52E cells were incubated with the blank vehicle [Dulbecco's modified Eagle's medium and F-12 [DMEM/F12] added with 10% fetal bovine serum [FBS]], 10 ng/ml TGF-beta1 alone or together with 100, 200 or 400microM tranilast for 48 h after incubation in medium containing 1% FBS for 24 h. Cell morphological changes were observed to confirm occurrence of EMT. Protein expressions of two typical markers of EMT, E-cadherin and alpha-smooth muscle actin [alpha-SMA], were assessed by western blotting and flow cytometry, respectively. Our results showed that TGF-beta1 induced spindle-like morphological transition, the loss of Ecadherin protein and upregulation of expression of alpha-SMA. However, the TGF-beta1-produced changes in cellular morphology, E-cadherin and alpha-SMA were inversed by tranlilast in concentration-dependent manner. Our findings indicate that tranilast can directly inhibit EMT. Thus, it may be implied that regulation of EMT be the target to prevent renal tubulointerstitial fibrosis.
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Index: IMEMR (Eastern Mediterranean) Main subject: Rats / Cadherins / Cell Line / Actins / Dose-Response Relationship, Drug / Epithelial-Mesenchymal Transition / Ortho-Aminobenzoates / Kidney Tubules, Proximal Limits: Animals Language: English Journal: Pak. J. Pharm. Sci. Year: 2014

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Index: IMEMR (Eastern Mediterranean) Main subject: Rats / Cadherins / Cell Line / Actins / Dose-Response Relationship, Drug / Epithelial-Mesenchymal Transition / Ortho-Aminobenzoates / Kidney Tubules, Proximal Limits: Animals Language: English Journal: Pak. J. Pharm. Sci. Year: 2014