Laminin alpha1 chain synthesis in the mouse developing lung: requirement for epithelial-mesenchymal contact and possible role in bronchial smooth muscle development.
Laminin alpha1 chain synthesis in the mouse developing lung: requirement for epithelial-mesenchymal contact and possible role in bronchial smooth muscle development.
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DOI：
10.1083/jcb.139.2.553
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发表时间：
1997-10-20
期刊：
影响因子：
--
通讯作者：
He L
中科院分区：
文献类型：
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作者：
Schuger L;Skubitz AP;Zhang J;Sorokin L;He L
层粘连蛋白是基底膜的主要成分，是由二硫键连接在一起的α、β和γ多肽链组成的异源三聚体。层粘连蛋白-1和层粘连蛋白-2均由β1和γ1链组成，α链不同，层粘连蛋白-1和层粘连蛋白-2的α链分别为α1和α2。本研究表明，虽然层粘连蛋白-1和-2在发育中的小鼠肺和由其衍生的上皮-间质共培养中合成，但上皮和间质单一培养失去了合成层粘连蛋白α -1链的能力。然而，层粘连蛋白α1链的合成在上皮-间质接触重建后恢复。细胞间接触是至关重要的，因为层粘连蛋白α1链在暴露于共培养条件培养基的单一培养中或在上皮-间充质共培养中检测不到，其中异型细胞-细胞接触被插入过滤器阻止。用蛋白分泌抑制剂brefeldin A处理共培养的免疫组织化学研究表明，上皮细胞和间充质细胞在异型细胞-细胞接触时均合成层粘连蛋白α1链。在一系列功能研究中，胚胎肺外植体在层粘连蛋白α1、α2和β/γ链单克隆抗体存在下培养。暴露于层粘连蛋白α1链单克隆抗体的肺外植体表现出支气管周围细胞形状的改变和平滑肌发育的减少，表现为平滑肌α肌动蛋白和desmin水平的降低。综上所述，我们的研究表明层粘连蛋白α1链的合成受上皮-间质相互作用的调节，并可能在气道平滑肌发育中发挥作用。
Laminins, the main components of basement membranes, are heterotrimers consisting of α, β, and γ polypeptide chains linked together by disulfide bonds. Laminins-1 and -2 are both composed of β1 and γ1 chains and differ from each other on their α chain, which is α1 and α2 for laminin-1 and -2, respectively. The present study shows that whereas laminins-1 and -2 are synthesized in the mouse developing lung and in epithelial–mesenchymal cocultures derived from it, epithelial and mesenchymal monocultures lose their ability to synthesize the laminin α1 chain. Synthesis of laminin α1 chain however returns upon re-establishment of epithelial–mesenchymal contact. Cell–cell contact is critical, since laminin α1 chain is not detected in monocultures exposed to coculture-conditioned medium or in epithelial–mesenchymal cocultures in which heterotypic cell–cell contact is prevented by an interposing filter. Immunohistochemical studies on cocultures treated with brefeldin A, an inhibitor of protein secretion, indicated both epithelial and mesenchymal cells synthesize laminin α1 chain upon heterotypic cell– cell contact. In a set of functional studies, embryonic lung explants were cultured in the presence of monoclonal antibodies to laminin α1, α2, and β/γ chains. Lung explants exposed to monoclonal antibodies to laminin α1 chain exhibited alterations in peribronchial cell shape and decreased smooth muscle development, as indicated by low levels of smooth muscle α actin and desmin. Taken together, our studies suggest that laminin α1 chain synthesis is regulated by epithelial–mesenchymal interaction and may play a role in airway smooth muscle development.