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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)...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PAGEPress Publications, Pavia, Italy
2013
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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 |
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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 |
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