Abstract:
We previously reported that tranilast can halt the pathogenesis of chronic cyclosporine nephrotoxicity in rats via the transforming growth factor-β (TGF-β) /Smad pathway, an important signaling system involved in epithelial-mesenchymal transition (EMT), but the exact underlying cellular mechanisms are not yet clear. Thus, by selecting [0]TGF−β1−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−β1 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-β1 alone or together with 100, 200 or 400µM 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 α-smooth muscle actin (α-SMA), were assessed by western blotting and flow cytometry, respectively. Our results showed that TGF-β1 induced spindle-like morphological transition, the loss of Ecadherin protein and upregulation of expression of α-SMA. However, the TGF-β1-produced changes in cellular morphology, E-cadherin and α-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.
Page(s):
51-55
DOI:
DOI not available
Published:
Journal: Pakistan Journal of Pharmaceutical Sciences, Volume: 27, Issue: 1, Year: 2014