title: Defect of hepatocyte growth factor secretion by fibroblasts in idiopathic pulmonary fibrosis.
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.
authors.affiliation: INSERM unit 408, Faculté Xavier Bichat, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, 16 rue Henri Huchard, 75877 Paris Cedex 18, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Marchand-Adam
authors.forename: Joëlle
authors.initials: J
authors.lastname: Marchal
authors.forename: Murielle
authors.initials: M
authors.lastname: Cohen
authors.forename: Paul
authors.initials: P
authors.lastname: Soler
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Gerard
authors.forename: Yves
authors.initials: Y
authors.lastname: Castier
authors.forename: Guy
authors.initials: G
authors.lastname: Lesèche
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
authors.forename: Hervé
authors.initials: H
authors.lastname: Mal
authors.forename: Michel
authors.initials: M
authors.lastname: Aubier
authors.forename: Monique
authors.initials: M
authors.lastname: Dehoux
authors.forename: Bruno
authors.initials: B
authors.lastname: Crestani
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000503:physiopathology*
chemical_list: D017228:Hepatocyte Growth Factor; D015232:Dinoprostone