Localization of avβ6 integrin- TGF-β1/Smad3, mTOR and PPARgg in experimental colorectal fibrosis

  • G. Latella | giolatel@tin.it University of L'Aquila, Italy.
  • A. Vetuschi University of L'Aquila, Italy.
  • R. Sferra University of L'Aquila, Italy.
  • S. Speca University of L'Aquila & National Institute of Health and Medical Research, Unit U995, Lille, Italy.
  • E. Gaudio La Sapienza University of Rome, Italy.

Abstract

A simultaneous action of several pro-fibrotic mediators appears relevant in the development of fibrosis. There are evidences that transforming growth factor-β (TGF-β)/Smad3 pathway forms with avβ6 integrin, mammalian target of Rapamycin (mTOR) and peroxisome proliferator-activated receptor-g (PPARg) a complex signalling network with extensive crosstalk and strong effects on fibrosis development. The present study evaluated the expression of TGFβ, Smad3, avβ6 integrin, mTOR and PPARg in 2, 4, 6-trinitrobenzenesulphonic acid (TNBS)-induced colorectal fibrosis in Smad3 wild-type (WT) and null mice. Smad3 WT mice treated with TNBS developed a marked colorectal fibrosis and showed a concomitant up-regulation of TGFβ, Smad3, avβ6 and mTOR and a reduction of PPARg expression. On the other hand, Smad3 Null mice similarly treated with TNBS did not develop fibrosis and showed a very low or even absent expression of TGFβ, Smad3, avβ6 and mTOR and a marked over-expression of PPARg. At the same time the expression of a-smooth muscle actin (a marker of activated myofibroblasts), collagen I-III and connective tissue growth factor (a downstream effector of TGFβ/Smad3-induced extracellular matrix proteins) were upregulated in Smad3 WT mice treated with TNBS compared to Null TNBS-treated mice. These preliminary results suggest a possible interaction between these pro-fibrotic molecules in the development of intestinal fibrosis.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Author Biographies

G. Latella, University of L'Aquila
Department of Life, Health and Environmental Sciences, Gastroenterology Unit
A. Vetuschi, University of L'Aquila
Department of Biotechnological and Applied Clinical Sciences
R. Sferra, University of L'Aquila
Department of Biotechnological and Applied Clinical Sciences
S. Speca, University of L'Aquila & National Institute of Health and Medical Research, Unit U995, Lille
Department of Life, Health and Environmental Sciences, Gastroenterology Unit
E. Gaudio, La Sapienza University of Rome
Department of Human Anatomy
Published
2013-12-04
Info
Issue
Section
Original Papers
Keywords:
Intestinal fibrosis, integrins, SMAD, mTOR, PPAR, IBD, TGF-β
Statistics
  • Abstract views: 2461

  • PDF: 377
  • HTML: 613
How to Cite
Latella, G., Vetuschi, A., Sferra, R., Speca, S., & Gaudio, E. (2013). Localization of avβ6 integrin- TGF-β1/Smad3, mTOR and PPARgg in experimental colorectal fibrosis. European Journal of Histochemistry, 57(4), e40. https://doi.org/10.4081/ejh.2013.e40

Most read articles by the same author(s)