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Host predisposition by endogenous Transforming Growth Factor-beta1 overexpression promotes pulmonary fibrosis following bleomycin injury.

Haider Y, Malizia AP, Keating DT, Birch M, Tomlinson A, Martin G, Ferguson MW, Doran PP, Egan JJ - J Inflamm (Lond) (2007)

Bottom Line: 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 TGFbeta1 as a key effector cytokine in the development of lung fibrosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Heart and Lung Transplant Program, Mater Misericordiae University Hospital, University College Dublin, Dublin. jegan@mater.ie.

ABSTRACT

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 TGFbeta1 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 TGFbeta1. 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 TGFbeta1 associated pulmonary fibrosis.

Conclusion: This data emphasises the importance of a host predisposition in the form of endogenous TGFbeta1, in the development of pulmonary fibrosis in response to an exogenous injury.

No MeSH data available.


Related in: MedlinePlus

Absence of lung fibrosis in TGFβ1 overexpressing mice. Figure A shows haematoxylin and eosin staining of Tr+ TGFβ1 transgenic lung tissue. Of note was the absence of fibrosis in transgenic mice. To determine the molecular events underpinning this process we determined the expression of TGFβ1 (B), Type I receptor for TGFβ1 (C) and the TGFβ1 Type II receptor (D) by immunohistochemistry. As can be seen TGFβ1 and its receptors are present in abundance in lung tissue from these mice, indicating a normal TGFβ1 signalling cascade in Tr+ pulmonary tissue.
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Figure 3: Absence of lung fibrosis in TGFβ1 overexpressing mice. Figure A shows haematoxylin and eosin staining of Tr+ TGFβ1 transgenic lung tissue. Of note was the absence of fibrosis in transgenic mice. To determine the molecular events underpinning this process we determined the expression of TGFβ1 (B), Type I receptor for TGFβ1 (C) and the TGFβ1 Type II receptor (D) by immunohistochemistry. As can be seen TGFβ1 and its receptors are present in abundance in lung tissue from these mice, indicating a normal TGFβ1 signalling cascade in Tr+ pulmonary tissue.

Mentions: Having demonstrated the molecular effect of TGFβ1 overexpression and its effect on mouse liver we examined the impact of Tr+ TGFβ1 transgenic expression on mouse lung. Of note was the finding that transgenic mouse lungs (Figure 3a) showed no evidence of de novo fibrosis at any time point studied.


Host predisposition by endogenous Transforming Growth Factor-beta1 overexpression promotes pulmonary fibrosis following bleomycin injury.

Haider Y, Malizia AP, Keating DT, Birch M, Tomlinson A, Martin G, Ferguson MW, Doran PP, Egan JJ - J Inflamm (Lond) (2007)

Absence of lung fibrosis in TGFβ1 overexpressing mice. Figure A shows haematoxylin and eosin staining of Tr+ TGFβ1 transgenic lung tissue. Of note was the absence of fibrosis in transgenic mice. To determine the molecular events underpinning this process we determined the expression of TGFβ1 (B), Type I receptor for TGFβ1 (C) and the TGFβ1 Type II receptor (D) by immunohistochemistry. As can be seen TGFβ1 and its receptors are present in abundance in lung tissue from these mice, indicating a normal TGFβ1 signalling cascade in Tr+ pulmonary tissue.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2169220&req=5

Figure 3: Absence of lung fibrosis in TGFβ1 overexpressing mice. Figure A shows haematoxylin and eosin staining of Tr+ TGFβ1 transgenic lung tissue. Of note was the absence of fibrosis in transgenic mice. To determine the molecular events underpinning this process we determined the expression of TGFβ1 (B), Type I receptor for TGFβ1 (C) and the TGFβ1 Type II receptor (D) by immunohistochemistry. As can be seen TGFβ1 and its receptors are present in abundance in lung tissue from these mice, indicating a normal TGFβ1 signalling cascade in Tr+ pulmonary tissue.
Mentions: Having demonstrated the molecular effect of TGFβ1 overexpression and its effect on mouse liver we examined the impact of Tr+ TGFβ1 transgenic expression on mouse lung. Of note was the finding that transgenic mouse lungs (Figure 3a) showed no evidence of de novo fibrosis at any time point studied.

Bottom Line: 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 TGFbeta1 as a key effector cytokine in the development of lung fibrosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Heart and Lung Transplant Program, Mater Misericordiae University Hospital, University College Dublin, Dublin. jegan@mater.ie.

ABSTRACT

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 TGFbeta1 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 TGFbeta1. 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 TGFbeta1 associated pulmonary fibrosis.

Conclusion: This data emphasises the importance of a host predisposition in the form of endogenous TGFbeta1, in the development of pulmonary fibrosis in response to an exogenous injury.

No MeSH data available.


Related in: MedlinePlus