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Am J Physiol Lung Cell Mol Physiol 288: L43-L51, 2005. First published September 24, 2004; doi:10.1152/ajplung.00096.2004
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FGF-18 is upregulated in the postnatal rat lung and enhances elastogenesis in myofibroblasts

Bernadette Chailley-Heu, Olivier Boucherat, Anne-Marie Barlier-Mur, and Jacques R. Bourbon

Physiopathologie et Thérapeutique Respiratoires, Institut National de la Santé et de la Recherche Médicale U492, Faculté de Médecine, Université Paris XII, Créteil, France

Submitted 17 March 2004 ; accepted in final form 31 August 2004

The fibroblast growth factors (FGFs) are key players in fetal lung development, but little is known about their status in postnatal lung. Here, we investigated the expression pattern of FGF-18 transcripts through the perinatal period and evidenced a sevenfold increase after birth that paralleled changes in elastin expression. In vitro, recombinant human (rh)FGF-18 had a mitogenic activity on day 21 fetal rat lung fibroblasts and stimulated its own expression in the latter, whereas FGF-2 inhibited it. At 50 or 100 ng/ml, rhFGF-18 increased the expression of {alpha}-smooth muscle actin ({alpha}-SMA; 2.5-fold), a characteristic marker of myofibroblasts, of tropoelastin (6.5-fold), of lysyl oxidase (2-fold), and of fibulins 1 and 5 (8- and 2.2-fold) in confluent fibroblasts isolated from fetal day 21 lung; similar results were obtained with fibroblasts from day 3 postnatal lungs. Elastin protein expression was also slightly increased in fetal fibroblasts. Lung analysis on day 4 in rat pups that had received rhFGF-18 (3 µg) on days 0 and 1 showed a 1.7-fold increase of tropoelastin transcripts, whereas {alpha}-SMA transcripts were unchanged. In contrast, rhFGF-2 markedly decreased expression of elastin in vitro and in vivo and of fibulin 5 in vitro. In addition, vitamin A, which is known to enhance alveolar development, elevated FGF-18 and elastin expressions in day 2 lungs, thus advancing the biological increase. We postulate that FGF-18 is involved in postnatal lung development through stimulating myofibroblast proliferation and differentiation.

lung development; elastin; lysyl oxidase; fibulin; {alpha}-smooth muscle actin; fibroblast growth factor-18



Address for reprint requests and other correspondence: B. Chailley-Heu, Institut National de la Santé et de la Recherche Médicale U492, Faculté de Médecine, 8 rue du Général Sarrail, 94010 Créteil cedex, France (E-mail: bernadette.chailley-heu{at}creteil.inserm.fr)




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