Cloning of rat fibrillin-2 cDNA and its role in branching morphogenesis of embryonic lung
Cloning of rat fibrillin-2 cDNA and its role in branching morphogenesis of embryonic lung
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DOI：
10.1006/dbio.1999.9331
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发表时间：
1999-08-01
影响因子：
2.7
通讯作者：
Kanwar, YS
中科院分区：
文献类型：
--
作者：
Yang, QW;Ota, K;Kanwar, YS
原纤维蛋白-2是一种细胞外基质蛋白。它与几种组织中的弹性纤维相关，并被认为是α v β 3整联蛋白的配体，α v β 3整联蛋白是已知的形态原。在这项研究中，研究了Escherin-2在肺发育中的作用。此外，大鼠hepatocin-2 cDNA的分离和测序，并确定其时空表达。它与人表皮生长因子-2的同源性接近88%，具有Ca 2+结合表皮生长因子样结构域、转化生长因子-β结合蛋白基序和两个RGD结合位点。北方印迹分析显示，一个类似于10-kb的转录本，和tropoelastin-2的表达发育调控，它取代了原弹性蛋白。在妊娠第13天，在间充质和上皮：间充质界面中表达了Escherin-2。从妊娠第13天至19天，它的表达增强，并局限于周围的气管支气管气道，而在出生后的时期减少。SDS-PAGE免疫沉淀显示与350-kDa相似的条带。用反义寡核苷酸处理肺移植物可诱导畸形发生。它们较小，有未发育的肺芽分支，塌陷的传导气道和松散膨胀的间充质。同时，在外植体中的抗肿瘤蛋白-2 mRNA，抗体反应性，和抗肿瘤蛋白-2特异性放射性掺入减少。抗-α v和-层粘连蛋白抗体反应性和它们各自掺入的特异性放射性没有改变。这些数据表明，在上皮细胞：间充质相互作用的背景下，肺纤维化蛋白-2调节肺的器官发生。可以想象的是，传导气道的塌陷也可能与干扰的呼吸道蛋白-2相互作用蛋白的生物学有关，即，弹性蛋白，后者对肺的正常生物生理学至关重要。(C)北京：科学出版社.
Fibrillin-2 is an extracellular matrix protein. It is associated with elastic fibers in several tissues and is believed to serve as a ligand for alpha v beta 3 integrin, the latter being a known morphogen. In this study, the role of fibrillin-2 in lung development was investigated. Also, rat fibrillin-2 cDNA was isolated and sequenced and its spatiotemporal expression determined. It had similar to 88% homology with human fibrillin-2 and had Ca2+ binding epidermal growth factor-like domains, transforming growth factor-beta binding protein motifs, and two RGD binding sites. Northern blot analysis revealed an similar to 10-kb transcript, and fibrillin-2 expression was developmentally regulated, and it paralleled that of tropoelastin. At day 13 of gestation, fibrillin-2 was expressed in the mesenchyme and at the epithelial:mesenchymal interface. From day 13 to 19 of gestation, its expression intensified and was confined around the tracheobronchial airways, while it lessened during the postnatal period. Immunoprecipitation revealed an similar to 350-kDa band by SDS-PAGE. Treatment with fibrillin-2 antisense oligodeoxynucleotide induced dysmorphogenesis of the lung explants. They were smaller and had rudimentary lung bud branches, collapsed conducting airways, and loose expanded mesenchyme. Concomitantly, fibrillin-2 mRNA, antibody reactivity in the explants, and fibrillin-2-specific radioincorporation were reduced. Anti-alpha v and -laminin antibody reactivity and their respective incorporated specific radioactivities were unaltered. These data indicate that fibrillin-2 modulates organogenesis of the lung in the context of epithelial: mesenchymal interactions. Conceivably, the collapse of the conducting airways may also be related to the perturbed biology of the fibrillin-2 interacting protein, i.e., elastin, the latter being critical for the normal biophysiology of the lungs. (C) 1999 Academic Press.