The pathogenesis of idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an appalling prognosis. The failure of anti-inflammatory therapies coupled with the observation that deranged epithelium overlies proliferative myofibroblasts to form the fibroblastic focus has lead to the emerging concept that IPF is a disease of deregulated epithelial-mesenchymal crosstalk. IPF is triggered by an as yet unidentified alveolar injury that leads to activation of transforming growth factor-β (TGF-β) and alveolar basement membrane disruption. In the presence of persisting injurious pathways, or disrupted repair pathways, activated TGF-β can lead to enhanced epithelial apoptosis and epithelial-to-mesenchymal transition (EMT) as well as fibroblast, and fibrocyte, transformation into myofibroblasts which are resistant to apoptosis. The resulting deposition of excess disrupted matrix by these myofibroblasts leads to the development of IPF.
Nottingham Respiratory Biomedical Research Unit, Clinical Sciences Building, Nottingham City Campus, Nottingham, UK.
William R
WR
Coward
Gauri
G
Saini
Gisli
G
Jenkins
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis; D001485:Basement Membrane / Q000473:pathology; D049109:Cell Proliferation; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000503:physiopathology*; D058628:Myofibroblasts / Q000473:pathology*; D011379:Prognosis; D011650:Pulmonary Alveoli / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D016212:Transforming Growth Factor beta