Dataset Information
An essential role for fibronectin extra type III domain A in pulmonary fibrosis.
Ontology highlight
ABSTRACT: Rationale
Tissue fibrosis is considered a dysregulated wound-healing response. Fibronectin containing extra type III domain A (EDA) is implicated in the regulation of wound healing. EDA-containing fibronectin is deposited during wound repair, and its presence precedes that of collagen.Objectives
To investigate the role of EDA-containing fibronectin in lung fibrogenesis.Methods
Primary lung fibroblasts from patients with idiopathic pulmonary fibrosis or from patients undergoing resection for lung cancer were assessed for EDA-containing fibronectin and alpha-smooth muscle actin (alpha-SMA) expression. Mice lacking the EDA domain of fibronectin and their wild-type littermates were challenged with the bleomycin model of lung fibrosis. Primary lung fibroblasts from these mice were assayed in vitro to determine the contribution of EDA-containing fibronectin to fibroblast phenotypes.Measurements and main results
Idiopathic pulmonary fibrosis lung fibroblasts produced markedly more EDA-containing fibronectin and alpha-SMA than control fibroblasts. EDA-null mice failed to develop significant fibrosis 21 days after bleomycin challenge, whereas wild-type controls developed the expected increase in total lung collagen. Histologic analysis of EDA-null lungs after bleomycin showed less collagen and fewer alpha-SMA-expressing myofibroblasts compared with that observed in wild-type mice. Failure to develop lung fibrosis in EDA-null mice correlated with diminished activation of latent transforming growth factor (TGF)-beta and decreased lung fibroblast responsiveness to active TGF-beta in vitro.Conclusions
The data show that EDA-containing fibronectin is essential for the fibrotic resolution of lung injury through TGF-beta activation and responsiveness, and suggest that EDA-containing fibronectin plays a critical role in tissue fibrogenesis.
SUBMITTER: Muro AF
PROVIDER: S-EPMC2267338 | biostudies-literature | 2008 Mar
REPOSITORIES: biostudies-literature
Publications
An essential role for fibronectin extra type III domain A in pulmonary fibrosis.
American journal of respiratory and critical care medicine 20071220 6
<h4>Rationale</h4>Tissue fibrosis is considered a dysregulated wound-healing response. Fibronectin containing extra type III domain A (EDA) is implicated in the regulation of wound healing. EDA-containing fibronectin is deposited during wound repair, and its presence precedes that of collagen.<h4>Objectives</h4>To investigate the role of EDA-containing fibronectin in lung fibrogenesis.<h4>Methods</h4>Primary lung fibroblasts from patients with idiopathic pulmonary fibrosis or from patients under ...[more]