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Pak J Pharm Sci. 2014 Jan;27(1):51-5.

Tranilast attenuates TGF-β1-induced epithelial-mesenchymal transition in the NRK-52E cells.

Author information

  • 1The Centre Laboratory, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China.
  • 2Department of Nephrology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China.
  • 3The Centre Laboratory, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China and The Emergency Center of Kunshan, Kunshan, Jiangsu, China.

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 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 E-cadherin 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.

PMID:
24374452
[PubMed - indexed for MEDLINE]
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