Interstitial fibrosis and growth factors.
Interstitial pulmonary fibrosis (IPF) is scarring of the lung caused by a variety of inhaled agents including mineral particles, organic dusts, and oxidant gases. The disease afflicts millions of individuals worldwide, and there are no effective therapeutic approaches. A major reason for this lack of useful treatments is that few of the molecular mechanisms of disease have been defined sufficiently to design appropriate targets for therapy. Our laboratory has focused on the molecular mechanisms through which three selected peptide growth factors could play a role in the development of IPF. Hundreds of growth factors and cytokines could be involved in the complex disease process. We are studying platelet-derived growth factor because it is the most potent mesenchymal cell mitogen yet described, transforming growth factor beta because it is a powerful inducer of extracellular matrix (scar tissue) components by mesenchymal cells, and tumor necrosis factor alpha because it is a pleiotropic cytokine that we and others have shown is essential for the development of IPF in animal models. This review describes some of the evidence from studies in humans, in animal models, and in vitro, that supports the growth factor hypothesis. The use of modern molecular and transgenic technologies could elucidate those targets that will allow effective therapeutic approaches.
Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine, and the Lung Biology Program, Tulane University Medical Center, New Orleans, Louisiana, USA.
J A
JA
Lasky
A R
AR
Brody
D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D017563:Lung Diseases, Interstitial / Q000209:etiology* / Q000276:immunology; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000276:immunology
D000393:Air Pollutants; D006133:Growth Substances