Laminin α1 chain synthesis in the mouse developing lung: Requirement for epithelial-mesenchymal contact and possible role in bronchial smooth muscle development

Lucia Schuger, Amy P Skubitz, Jun Zhang, Lydia Sorokin, Li He

Research output: Contribution to journalArticle

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Abstract

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 α 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.

Original languageEnglish (US)
Pages (from-to)553-562
Number of pages10
JournalJournal of Cell Biology
Volume139
Issue number2
DOIs
StatePublished - Oct 20 1997

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Muscle Development
Smooth Muscle
Lung
Coculture Techniques
Laminin
Monoclonal Antibodies
Brefeldin A
laminin 1
Desmin
Cell Shape
Conditioned Culture Medium
Basement Membrane
Disulfides
Actins
Epithelial Cells
Peptides

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Laminin α1 chain synthesis in the mouse developing lung : Requirement for epithelial-mesenchymal contact and possible role in bronchial smooth muscle development. / Schuger, Lucia; Skubitz, Amy P; Zhang, Jun; Sorokin, Lydia; He, Li.

In: Journal of Cell Biology, Vol. 139, No. 2, 20.10.1997, p. 553-562.

Research output: Contribution to journalArticle

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