Expression of the integrin subunit α8 in murine lung development

Expression of the integrin subunit α8 in murine lung development
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DOI:
10.1177/002215540305101008
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发表时间:
2003-10-01
影响因子:
3.2
通讯作者:
Schnapp, LM
Schnapp, LM
中科院分区:
生物学3区
文献类型:
--
作者:
Wagner, TE;Frevert, CW;Schnapp, LM

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细胞和细胞外基质(ECM)蛋白之间复杂的相互作用对肺发育至关重要。整合素是这种相互作用的关键调节剂。整联蛋白亚基α 8与β(1)-亚基结合形成结合RGD的整联蛋白。我们以前的研究表明,在成人肺中,α 8在收缩性间质细胞和平滑肌细胞中表达,并在肺损伤中上调。为了深入了解alpha8在肺发育过程中的功能,我们研究了alpha8在整个小鼠肺发育过程中的时空表达。我们比较了α 8与α-平滑肌肌动蛋白(α SMA)、纤连蛋白(α 8配体)和细胞角蛋白的分布。α 8与α SMA和纤连蛋白共定位于支气管周围和血管周围区域。在所有阶段,α 8免疫反应性弥漫性检测间质中,除了周围的细胞远端,新形成的气道。α 8、α SMA和纤连蛋白在肺泡期共定位于次级隔膜的尖端。我们得出结论,α 8是肺间充质细胞在发育早期开始的标志物。α 8也是平滑肌细胞的标志物,早在α SMA表达。α 8与纤连蛋白的共定位表明在分支形态发生中的作用。此外,α 8可能通过调节从细胞外基质到肺泡肌成纤维细胞的信号参与继发性分隔。
The complex interplay between cells and extracellular matrix (ECM) proteins is critical for lung development. Integrins are key modulators of this interaction. The integrin subunit alpha8 associates with the beta(1)-subunit to form an RGD-binding integrin. We previously showed that, in adult lung, alpha8 is expressed in contractile interstitial cells and smooth muscle cells and is upregulated in lung injury. To gain insight into the function of alpha8 during lung development, we examined the spatiotemporal expression of alpha8 throughout murine lung development. We compared the distribution of alpha8 with alpha-smooth muscle actin (alphaSMA), fibronectin (alpha8 ligand), and cytokeratin. alpha8 co-localized with alphaSMA and fibronectin in the peribronchial and perivascular regions. In all stages, alpha8 immunoreactivity was detected diffusely in the mesenchyme except for cells surrounding distal, newly forming airways. alpha8, alphaSMA, and fibronectin co-localized at tips of secondary septae in the alveolar stage. We conclude that alpha8 is marker for lung mesenchymal cells starting early in development. alpha8 is also a marker for smooth muscle cells, expressed as early as alphaSMA. Co-localization of alpha8 with fibronectin suggests a role in branching morphogenesis. Furthermore, alpha8 may participate in secondary septation by modulating signals from the extracellular matrix to alveolar myofibroblasts.