FGF signaling is required for myofibroblast differentiation during alveolar regeneration
FGF signaling is required for myofibroblast differentiation during alveolar regeneration
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DOI：
10.1152/ajplung.00008.2009
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发表时间：
2009-08-01
影响因子：
4.9
通讯作者：
Gale, Emily
中科院分区：
文献类型：
--
作者：
Perl, Anne-Karina T.;Gale, Emily
佩尔（Perl）AK，盖尔（Gale）E。在肺泡再生过程中，成肌纤维细胞分化需要成纤维细胞生长因子（FGF）信号传导。《美国生理学杂志 - 肺细胞与分子生理学》297卷：L299 - L308，2009年。首次发表于2009年6月5日；doi:10.1152/ajplung.00008.2009。 - 已使用详细的形态测量技术以及生长因子及其受体的功能缺失方法在啮齿动物中研究了正常的肺泡形成。然而，这些生长因子如何指导次级隔膜的形成仍不清楚。我们先前开发了一种转基因小鼠模型，在该模型中，产前时期可溶性显性负性FGF受体（dnFGFR）的表达导致肺泡隔膜形成减少以及随后的肺泡简化。视黄酸（RA）是维生素A的一种具有生物活性的衍生物，可诱导成年啮齿动物的肺泡再生。在本研究中，我们证明RA在该转基因小鼠模型中诱导肺泡再分隔，并且成年小鼠的肺泡再形成依赖于FGF。在RA治疗14天后，肺实质的增殖（肺再生长的必要前提）增强，并且不受dnFGFR表达的影响。在正常肺发育过程中，次级隔膜的形成与α - 平滑肌肌动蛋白（α - SMA）阳性的间质成肌纤维细胞的短暂存在有关。RA治疗完成一周后，在间质成纤维细胞中检测到α - SMA表达，这支持了RA诱导的肺泡再形成重现正常肺发育过程中分隔的某些方面这一概念。dnFGFR的表达阻断了肺泡再形成，表现为血小板衍生生长因子受体 - α（PDGFRα）阳性细胞增加，α - SMA阳性细胞减少。综上所述，我们的数据表明，在血小板衍生生长因子受体 - α阳性的成肌纤维细胞祖细胞中诱导α - SMA以及肺泡再生的进展需要FGF信号传导。
Perl AK, Gale E. FGF signaling is required for myofibroblast differentiation during alveolar regeneration. Am J Physiol Lung Cell Mol Physiol 297: L299-L308, 2009. First published June 5, 2009; doi:10.1152/ajplung.00008.2009.-Normal alveolarization has been studied in rodents using detailed morphometric techniques and loss of function approaches for growth factors and their receptors. However, it remains unclear how these growth factors direct the formation of secondary septae. We have previously developed a transgenic mouse model in which expression of a soluble dominant-negative FGF receptor (dnFGFR) in the prenatal period results in reduced alveolar septae formation and subsequent alveolar simplification. Retinoic acid ( RA), a biologically active derivative of vitamin A, can induce regeneration of alveoli in adult rodents. In this study, we demonstrate that RA induces alveolar reseptation in this transgenic mouse model and that realveolarization in adult mice is FGF dependent. Proliferation in the lung parenchyma, an essential prerequisite for lung re-growth was enhanced after 14 days of RA treatment and was not influenced by dnFGFR expression. During normal lung development, formation of secondary septae is associated with the transient presence of alpha-smooth muscle actin (alpha SMA)-positive interstitial myofibroblasts. One week after completion of RA treatment, alpha SMA expression was detected in interstitial fibroblasts, supporting the concept that RA-initiated realveolarization recapitulates aspects of septation that occur during normal lung development. Expression of dnFGFR blocked realveolarization with increased PDGF receptor-alpha (PDGFR alpha)-positive cells and decreased alpha SMA-positive cells. Taken together, our data demonstrate that FGF signaling is required for the induction of alpha SMA in the PDGFR alpha-positive myofibroblast progenitor and the progression of alveolar regeneration.