Cargando…

Localization of αυβ6 Integrin-TGF-β1/Smad3, mTOR and PPARγ in Experimental Colorectal Fibrosis

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 αvβ6 integrin, mammalian target of Rapamycin (mTOR) and peroxisome proliferator-activated receptor-γ (PPARγ)...

Descripción completa

Detalles Bibliográficos
Autores principales: Latella, G., Vetuschi, A., Sferra, R., Speca, S., Gaudio, E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PAGEPress Publications, Pavia, Italy 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896042/
https://www.ncbi.nlm.nih.gov/pubmed/24441193
http://dx.doi.org/10.4081/ejh.2013.e40
_version_ 1782300044707233792
author Latella, G.
Vetuschi, A.
Sferra, R.
Speca, S.
Gaudio, E.
author_facet Latella, G.
Vetuschi, A.
Sferra, R.
Speca, S.
Gaudio, E.
author_sort Latella, G.
collection PubMed
description 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 αvβ6 integrin, mammalian target of Rapamycin (mTOR) and peroxisome proliferator-activated receptor-γ (PPARγ) a complex signalling network with extensive crosstalk and strong effects on fibrosis development. The present study evaluated the expression of TGFβ, Smad3, αvβ6 integrin, mTOR and PPARγ 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, αvβ6 and mTOR and a reduction of PPARγ 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, αvβ6 and mTOR and a marked over-expression of PPARγ. At the same time the expression of α-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 up-regulated 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.
format Online
Article
Text
id pubmed-3896042
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher PAGEPress Publications, Pavia, Italy
record_format MEDLINE/PubMed
spelling pubmed-38960422014-01-24 Localization of αυβ6 Integrin-TGF-β1/Smad3, mTOR and PPARγ in Experimental Colorectal Fibrosis Latella, G. Vetuschi, A. Sferra, R. Speca, S. Gaudio, E. Eur J Histochem Original Paper 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 αvβ6 integrin, mammalian target of Rapamycin (mTOR) and peroxisome proliferator-activated receptor-γ (PPARγ) a complex signalling network with extensive crosstalk and strong effects on fibrosis development. The present study evaluated the expression of TGFβ, Smad3, αvβ6 integrin, mTOR and PPARγ 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, αvβ6 and mTOR and a reduction of PPARγ 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, αvβ6 and mTOR and a marked over-expression of PPARγ. At the same time the expression of α-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 up-regulated 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. PAGEPress Publications, Pavia, Italy 2013-12-04 /pmc/articles/PMC3896042/ /pubmed/24441193 http://dx.doi.org/10.4081/ejh.2013.e40 Text en ©Copyright G. Latella et al. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Paper
Latella, G.
Vetuschi, A.
Sferra, R.
Speca, S.
Gaudio, E.
Localization of αυβ6 Integrin-TGF-β1/Smad3, mTOR and PPARγ in Experimental Colorectal Fibrosis
title Localization of αυβ6 Integrin-TGF-β1/Smad3, mTOR and PPARγ in Experimental Colorectal Fibrosis
title_full Localization of αυβ6 Integrin-TGF-β1/Smad3, mTOR and PPARγ in Experimental Colorectal Fibrosis
title_fullStr Localization of αυβ6 Integrin-TGF-β1/Smad3, mTOR and PPARγ in Experimental Colorectal Fibrosis
title_full_unstemmed Localization of αυβ6 Integrin-TGF-β1/Smad3, mTOR and PPARγ in Experimental Colorectal Fibrosis
title_short Localization of αυβ6 Integrin-TGF-β1/Smad3, mTOR and PPARγ in Experimental Colorectal Fibrosis
title_sort localization of αυβ6 integrin-tgf-β1/smad3, mtor and pparγ in experimental colorectal fibrosis
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896042/
https://www.ncbi.nlm.nih.gov/pubmed/24441193
http://dx.doi.org/10.4081/ejh.2013.e40
work_keys_str_mv AT latellag localizationofaub6integrintgfb1smad3mtorandpparginexperimentalcolorectalfibrosis
AT vetuschia localizationofaub6integrintgfb1smad3mtorandpparginexperimentalcolorectalfibrosis
AT sferrar localizationofaub6integrintgfb1smad3mtorandpparginexperimentalcolorectalfibrosis
AT specas localizationofaub6integrintgfb1smad3mtorandpparginexperimentalcolorectalfibrosis
AT gaudioe localizationofaub6integrintgfb1smad3mtorandpparginexperimentalcolorectalfibrosis