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1 Faculte de Medecine, Universite Paris XII, Inserm U492, Creteil, France
* To whom correspondence should be addressed. E-mail: bernadette.chailley-heu{at}creteil.inserm.fr.
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 FGF18 transcripts through the perinatal period and evidenced a 7-fold increase after birth that paralleled changes in elastin expression. In vitro, rhFGF18 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 100ng/ml, rhFGF18 increased the expression of 
-smooth muscle actin (-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 rhFGF18 (3µg) on days 0 and 1 showed a 1.7-fold increase of tropoelastin transcripts, whereas -SMA transcripts were unchanged. In contrast, rhFGF2 markedly decreased expression of elastin in vitro and in vivo and of fibulin5 in vitro. In addition, vitamin A that is known to enhance alveolar development elevated FGF18 and elastin expressions in day 2 lungs, thus advancing the biological increase. We postulate that FGF18 is involved in postnatal lung development through stimulating myofibroblast proliferation and differentiation.
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