Limits...
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

TGFβ1 overexpression induces severe liver fibrosis. A. Shown are representative micrographs following haematoxylin/eosin staining indicating severe liver fibrosis in TGFβ1 transgene expressing mice. B shows normal Tr- wild type mice liver tissue stained by haematoxylin/eosin. C. The deposition of the pro-collagen, reticulin, was also determined using specific monoclonal antibody anty-reticulin by immunohistochemistry in Tr- WT mice liver tissue sections. D. Whilst low abundance staining is seen in wild type liver, expression of reticulin is dramatically enhanced in the Tr+ TGFβ1 transgenic mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2169220&req=5

Figure 2: TGFβ1 overexpression induces severe liver fibrosis. A. Shown are representative micrographs following haematoxylin/eosin staining indicating severe liver fibrosis in TGFβ1 transgene expressing mice. B shows normal Tr- wild type mice liver tissue stained by haematoxylin/eosin. C. The deposition of the pro-collagen, reticulin, was also determined using specific monoclonal antibody anty-reticulin by immunohistochemistry in Tr- WT mice liver tissue sections. D. Whilst low abundance staining is seen in wild type liver, expression of reticulin is dramatically enhanced in the Tr+ TGFβ1 transgenic mice.

Mentions: Tr+ transgenic mouse livers were histologically abnormal as early as 1 month, though the most marked changes were seen from 3 months onwards. This consisted of extensive cellular degeneration, vacuolisation, fibrosis and architectural disruption (Figure 2a), compared to Tr- wild type mouse liver (Figure 2b). Staining for the pre-collagen, reticulin signalling was higher in transgenic mice tissue than wild type, confirming the presence of ongoing tissue fibrosis (Figure 2c–d). Tissue changes were most pronounced in the line 25 mice, but also present in line 18 mice, while wild type mice had normal liver architecture and normal reticulin levels.


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)

TGFβ1 overexpression induces severe liver fibrosis. A. Shown are representative micrographs following haematoxylin/eosin staining indicating severe liver fibrosis in TGFβ1 transgene expressing mice. B shows normal Tr- wild type mice liver tissue stained by haematoxylin/eosin. C. The deposition of the pro-collagen, reticulin, was also determined using specific monoclonal antibody anty-reticulin by immunohistochemistry in Tr- WT mice liver tissue sections. D. Whilst low abundance staining is seen in wild type liver, expression of reticulin is dramatically enhanced in the Tr+ TGFβ1 transgenic mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: TGFβ1 overexpression induces severe liver fibrosis. A. Shown are representative micrographs following haematoxylin/eosin staining indicating severe liver fibrosis in TGFβ1 transgene expressing mice. B shows normal Tr- wild type mice liver tissue stained by haematoxylin/eosin. C. The deposition of the pro-collagen, reticulin, was also determined using specific monoclonal antibody anty-reticulin by immunohistochemistry in Tr- WT mice liver tissue sections. D. Whilst low abundance staining is seen in wild type liver, expression of reticulin is dramatically enhanced in the Tr+ TGFβ1 transgenic mice.
Mentions: Tr+ transgenic mouse livers were histologically abnormal as early as 1 month, though the most marked changes were seen from 3 months onwards. This consisted of extensive cellular degeneration, vacuolisation, fibrosis and architectural disruption (Figure 2a), compared to Tr- wild type mouse liver (Figure 2b). Staining for the pre-collagen, reticulin signalling was higher in transgenic mice tissue than wild type, confirming the presence of ongoing tissue fibrosis (Figure 2c–d). Tissue changes were most pronounced in the line 25 mice, but also present in line 18 mice, while wild type mice had normal liver architecture and normal reticulin levels.

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