Cargando…
Host predisposition by endogenous Transforming Growth Factor-β1 overexpression promotes pulmonary fibrosis following bleomycin injury
BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a progressive diffuse disease involving the lung parenchyma. Despite recent advances, the molecular mechanisms of the initiation and progression of this disease remain elusive. Previous studies have demonstrated TGFβ1 as a key effector cytokine in t...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2007
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169220/ https://www.ncbi.nlm.nih.gov/pubmed/17883846 http://dx.doi.org/10.1186/1476-9255-4-18 |
_version_ | 1782144850695553024 |
---|---|
author | Haider, Yussef Malizia, Andrea P Keating, Dominic T Birch, Mary Tomlinson, Annette Martin, Gail Ferguson, Mark WJ Doran, Peter P Egan, Jim J |
author_facet | Haider, Yussef Malizia, Andrea P Keating, Dominic T Birch, Mary Tomlinson, Annette Martin, Gail Ferguson, Mark WJ Doran, Peter P Egan, Jim J |
author_sort | Haider, Yussef |
collection | PubMed |
description | BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a progressive diffuse disease involving the lung parenchyma. Despite recent advances, the molecular mechanisms of the initiation and progression of this disease remain elusive. Previous studies have demonstrated TGFβ1 as a key effector cytokine in the development of lung fibrosis. METHODS: In this study we have used a transgenic mouse based strategy to identify the effect of overexpression of this key effector mediator on the development of pulmonary fibrosis in response to exogenous injury. We bred two lines (line 25 and 18) of transgenic mice (Tr+) that overexpressed active TGFβ1. Three-month old transgenic and wild type mice were subsequently wounded with intraperitoneal bleomycin. Mice were sacrificed at 6 weeks post-bleomycin and their lungs analysed histologically and biochemically. RESULTS: The severity of lung fibrosis was significantly greater in the Tr+ mice compared to the wild type mice. Using an oligonucleotide microarray based strategy we identified discrete patterns of gene expression contributing to TGFβ1 associated pulmonary fibrosis. CONCLUSION: This data emphasises the importance of a host predisposition in the form of endogenous TGFβ1, in the development of pulmonary fibrosis in response to an exogenous injury. |
format | Text |
id | pubmed-2169220 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-21692202007-12-29 Host predisposition by endogenous Transforming Growth Factor-β1 overexpression promotes pulmonary fibrosis following bleomycin injury Haider, Yussef Malizia, Andrea P Keating, Dominic T Birch, Mary Tomlinson, Annette Martin, Gail Ferguson, Mark WJ Doran, Peter P Egan, Jim J J Inflamm (Lond) Research BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a progressive diffuse disease involving the lung parenchyma. Despite recent advances, the molecular mechanisms of the initiation and progression of this disease remain elusive. Previous studies have demonstrated TGFβ1 as a key effector cytokine in the development of lung fibrosis. METHODS: In this study we have used a transgenic mouse based strategy to identify the effect of overexpression of this key effector mediator on the development of pulmonary fibrosis in response to exogenous injury. We bred two lines (line 25 and 18) of transgenic mice (Tr+) that overexpressed active TGFβ1. Three-month old transgenic and wild type mice were subsequently wounded with intraperitoneal bleomycin. Mice were sacrificed at 6 weeks post-bleomycin and their lungs analysed histologically and biochemically. RESULTS: The severity of lung fibrosis was significantly greater in the Tr+ mice compared to the wild type mice. Using an oligonucleotide microarray based strategy we identified discrete patterns of gene expression contributing to TGFβ1 associated pulmonary fibrosis. CONCLUSION: This data emphasises the importance of a host predisposition in the form of endogenous TGFβ1, in the development of pulmonary fibrosis in response to an exogenous injury. BioMed Central 2007-09-20 /pmc/articles/PMC2169220/ /pubmed/17883846 http://dx.doi.org/10.1186/1476-9255-4-18 Text en Copyright © 2007 Haider et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Haider, Yussef Malizia, Andrea P Keating, Dominic T Birch, Mary Tomlinson, Annette Martin, Gail Ferguson, Mark WJ Doran, Peter P Egan, Jim J Host predisposition by endogenous Transforming Growth Factor-β1 overexpression promotes pulmonary fibrosis following bleomycin injury |
title | Host predisposition by endogenous Transforming Growth Factor-β1 overexpression promotes pulmonary fibrosis following bleomycin injury |
title_full | Host predisposition by endogenous Transforming Growth Factor-β1 overexpression promotes pulmonary fibrosis following bleomycin injury |
title_fullStr | Host predisposition by endogenous Transforming Growth Factor-β1 overexpression promotes pulmonary fibrosis following bleomycin injury |
title_full_unstemmed | Host predisposition by endogenous Transforming Growth Factor-β1 overexpression promotes pulmonary fibrosis following bleomycin injury |
title_short | Host predisposition by endogenous Transforming Growth Factor-β1 overexpression promotes pulmonary fibrosis following bleomycin injury |
title_sort | host predisposition by endogenous transforming growth factor-β1 overexpression promotes pulmonary fibrosis following bleomycin injury |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169220/ https://www.ncbi.nlm.nih.gov/pubmed/17883846 http://dx.doi.org/10.1186/1476-9255-4-18 |
work_keys_str_mv | AT haideryussef hostpredispositionbyendogenoustransforminggrowthfactorb1overexpressionpromotespulmonaryfibrosisfollowingbleomycininjury AT maliziaandreap hostpredispositionbyendogenoustransforminggrowthfactorb1overexpressionpromotespulmonaryfibrosisfollowingbleomycininjury AT keatingdominict hostpredispositionbyendogenoustransforminggrowthfactorb1overexpressionpromotespulmonaryfibrosisfollowingbleomycininjury AT birchmary hostpredispositionbyendogenoustransforminggrowthfactorb1overexpressionpromotespulmonaryfibrosisfollowingbleomycininjury AT tomlinsonannette hostpredispositionbyendogenoustransforminggrowthfactorb1overexpressionpromotespulmonaryfibrosisfollowingbleomycininjury AT martingail hostpredispositionbyendogenoustransforminggrowthfactorb1overexpressionpromotespulmonaryfibrosisfollowingbleomycininjury AT fergusonmarkwj hostpredispositionbyendogenoustransforminggrowthfactorb1overexpressionpromotespulmonaryfibrosisfollowingbleomycininjury AT doranpeterp hostpredispositionbyendogenoustransforminggrowthfactorb1overexpressionpromotespulmonaryfibrosisfollowingbleomycininjury AT eganjimj hostpredispositionbyendogenoustransforminggrowthfactorb1overexpressionpromotespulmonaryfibrosisfollowingbleomycininjury |