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  • Title: Lefty antagonises TGF-beta1 induced epithelial-mesenchymal transition in tubular epithelial cells.
    Author: Mariasegaram M, Tesch GH, Verhardt S, Hurst L, Lan HY, Nikolic-Paterson DJ.
    Journal: Biochem Biophys Res Commun; 2010 Mar 19; 393(4):855-9. PubMed ID: 20171171.
    Abstract:
    Lefty is a novel member of the transforming growth factor (TGF) supergene family which has the potential to antagonise actions of TGF-beta1 - the main factor driving fibrotic disease in the kidney and in other organs. TGF-beta1 can induce fibrosis through several mechanisms, including epithelial-mesenchymal transition (EMT) which contributes to myofibroblast accumulation in the renal interstitium. This study examined whether Lefty can antagonise TGF-beta1 mediated EMT. A rat tubular epithelial cell line (NRK52E) was stably transfected with a Lefty expression plasmid (52E-Lefty) or control plasmid (52E-Control). 52E-Control cells underwent TGF-beta1 induced EMT with up-regulation of alpha-smooth muscle actin (alpha-SMA), down-regulation of E-cadherin, and transition to an elongated fibroblast-like morphology. In contrast, 52E-Lefty cells were substantially protected from TGF-beta1 induced EMT. Analysis of signalling pathways showed that 52E-Lefty cells had a marked reduction in TGF-beta1 induced Smad activity and suppression of the secondary phase of JNK (but not p38) signalling. Treatment of NRK52E cells with a JNK inhibitor was shown to suppress TGF-beta1 induced EMT. In conclusion, Lefty can antagonise TGF-beta1 mediated EMT in renal tubular epithelial cells. Lefty may have potential as an anti-fibrotic molecule in the treatment of renal fibrosis.
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