The myofibroblast in pulmonary fibrosis.
The pathogenesis of pulmonary fibrosis remains incompletely understood. Studies of associated inflammation have led to the discovery of a number of cytokines and chemokines that are found to be important either directly or indirectly for the fibrotic process. However, the importance of inflammation in pulmonary fibrosis is unclear, and at the time of diagnosis the inflammatory component is variable and usually not responsive to anti-inflammatory therapeutic agents. Patients usually exhibit evidence of active fibrosis with increased numbers of activated fibroblasts, many of which have the phenotypic characteristics of myofibroblasts. At these sites, increased amounts of extracellular matrix deposition are evident with effacement of the normal alveolar architecture. Animal model studies show the myofibroblast to be the primary source of type I collagen gene expression in active fibrotic sites. In vitro studies show differentiation of these cells from fibroblasts under the influence of certain cytokines but indicate their susceptibility to nitric oxide-mediated apoptosis. In addition to promoting myofibroblast differentiation, transforming growth factor-beta1 provides protection against apoptosis. Thus, this well-known fibrogenic cytokine is important both for the emergence of the myofibroblast and its survival against apoptotic stimuli. This is consistent with the critical importance of this cytokine in diverse models of fibrosis in various tissues. In view of these properties, the persistence or prolonged survival of the myofibroblast may be key to understanding why certain forms of lung injury may result in progressive disease, terminating in end-stage disease.
Phan
Sem H
SH
Department of Pathology, University of Michigan, Ann Arbor, MI 48109-0602, USA. shphan@umich.edu
D017209:Apoptosis / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D011650:Pulmonary Alveoli / Q000473:pathology / Q000503:physiopathology; D011658:Pulmonary Fibrosis / Q000473:pathology / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000276:immunology*; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1