首页> 外文期刊>American Journal of Physiology >FGF-18 is upregulated in the postnatal rat lung and enhances elastogenesis in myofibroblasts.
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FGF-18 is upregulated in the postnatal rat lung and enhances elastogenesis in myofibroblasts.

机译:FGF-18在出生后的大鼠肺中上调,并增强了成肌纤维细胞中的弹性生成。

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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 microg) 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.
机译:成纤维细胞生长因子(FGFs)是胎儿肺发育的关键因素,但对其在产后肺中的状态知之甚少。在这里,我们调查了整个围产期FGF-18转录物的表达模式,并证明了出生后与弹性蛋白表达变化平行的七倍增长。在体外,重组人(rh)FGF-18在第21天对胎儿大鼠肺成纤维细胞具有促有丝分裂活性,并在后者中刺激其自身表达,而FGF-2对其抑制。在50 ng / ml或100 ng / ml时,rhFGF-18增加了成肌纤维细胞,原弹性蛋白(6.5倍),赖氨酰氧化酶(2-的特征标记)的α平滑肌肌动蛋白(α-SMA; 2.5倍)的表达。从胎儿第21天肺分离的融合成纤维细胞中,纤维蛋白1和5(8倍和2.2倍);出生后第3天的肺部成纤维细胞获得了相似的结果。胎儿成纤维细胞中的弹性蛋白蛋白表达也略有增加。在第0天和第1天接受rhFGF-18(3微克)的大鼠幼崽在第4天的肺部分析显示,原弹性蛋白转录本增加了1.7倍,而α-SMA转录本则没有变化。相反,rhFGF-2在体外和体内显着降低了弹性蛋白的表达,而在体外则降低了纤维蛋白5的表达。此外,已知可增强肺泡发育的维生素A在第2天的肺中可提高FGF-18和弹性蛋白的表达,从而促进生物学增长。我们推测FGF-18通过刺激成肌纤维细胞的增殖和分化参与了产后肺的发育。

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