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Deficient repair response of IPF fibroblasts in a co-culture model of epithelial injury and repair.


ABSTRACT:

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive disorder marked by relentless fibrosis and damage of the lung architecture. A growing body of evidence now suggests that IPF progresses as a result of aberrant epithelial-fibroblast crosstalk. Injured epithelia are a major source of growth factors such as PDGF which guide resident fibroblasts to injury sites.

Results

In this study, we utilized a novel co-culture system to investigate the effect of fibroblast phenotype on their response to epithelial injury. Fibroblasts from normal lungs (NHLF) responded to epithelial injury and populated the wound site forming a fibroblast plug/mechanical barrier which prevented epithelial wound closure. IPF fibroblasts were impaired in their response to epithelial injury. They also expressed reduced PDGFR? compared to NHLFs and were defective towards PDGF-AA mediated directional movement. Neutralization of PDGF-AA and pan-PDGF but not PDGF-BB reduced the injury response of NHLFs thereby preventing the formation of the mechanical barrier and promoting epithelial wound closure. Co-culture of epithelial cells with IPF fibroblasts led to marked increase in the levels of pro-fibrotic growth factors - bFGF and PDGF and significant depletion of anti-fibrotic HGF in the culture medium. Furthermore, IPF fibroblasts but not NHLFs induced a transient increase in mesenchymal marker expression in the wound lining epithelial cells. This was accompanied by increased migration and faster wound closure in co-cultures with IPF fibroblasts.

Conclusions

Our data demonstrate that the IPF fibroblasts have an aberrant repair response to epithelial injury.

SUBMITTER: Prasad S 

PROVIDER: S-EPMC4021590 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Deficient repair response of IPF fibroblasts in a co-culture model of epithelial injury and repair.

Prasad Sony S   Hogaboam Cory M CM   Jarai Gabor G  

Fibrogenesis & tissue repair 20140429


<h4>Background</h4>Idiopathic pulmonary fibrosis (IPF) is a progressive disorder marked by relentless fibrosis and damage of the lung architecture. A growing body of evidence now suggests that IPF progresses as a result of aberrant epithelial-fibroblast crosstalk. Injured epithelia are a major source of growth factors such as PDGF which guide resident fibroblasts to injury sites.<h4>Results</h4>In this study, we utilized a novel co-culture system to investigate the effect of fibroblast phenotype  ...[more]

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