Defect of hepatocyte growth factor secretion by fibroblasts in idiopathic pulmonary fibrosis.
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| Abstract |
Hepatocyte growth factor (HGF) is a growth factor that protects alveolar epithelial cells from pulmonary fibrosis in various animal models. We compared in vitro HGF production by human lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF, n = 8) and from control subjects (n = 6). Basal HGF secretion by IPF fibroblasts was decreased by 50% when compared with control fibroblasts (p < 0.05). HGF was secreted mainly in the cleaved mature form, both in IPF and control fibroblasts. HGF messenger RNA levels were reduced in IPF fibroblasts. Prostaglandin (PG) E2 secretion by IPF fibroblasts was low when compared with control subjects (p < 0.05). After the addition of PGE2 (10-6 M) or dibutyryl cyclic AMP (10-3 M), HGF secretion by IPF fibroblasts reached the level of control subjects. Inhibition of PGE2 synthesis with indomethacin reduced HGF secretion by control fibroblasts but had no effect on IPF fibroblasts. HGF secretion by control fibroblasts was also slightly inhibited by transforming growth factor (TGF)-beta1 and stimulated by anti-TGF-beta antibody, whereas both agents had no effect on IPF fibroblasts. Our results demonstrate a defect in HGF production by IPF fibroblasts that seems secondary to a defect in PGE2 secretion.
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| Authors | Sylvain Marchand-Adam, Joëlle Marchal, Murielle Cohen, Paul Soler, Bénédicte Gerard, Yves Castier, Guy Lesèche, Dominique Valeyre, Hervé Mal, Michel Aubier, Monique Dehoux, Bruno Crestani |
| Journal | American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 168 Issue 10 Pg. 1156-61 (Nov 15 2003) ISSN: 1073-449X [Print] United States |
| PMID | 12947024 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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