The Development of Integrin Alpha-8 Deficient Lungs Shows Reduced and Altered Branching and a Correction of the Phenotype During Alveolarization
Cremona TP, Hartner A, Schittny JC (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 11
DOI: 10.3389/fphys.2020.530635
Abstract
Lung development involves epithelial-mesenchymal interactions and integrins represent one of the key elements. These extracellular matrix receptors form hetero-dimers of alpha and beta subunits. The integrin alpha 8 beta 1 is highly expressed in mouse tissues, including lung. It forms a cellular receptor for fibronectin, vitronectin, osteopontin, nephronectin, and tenascin-C. This study aims to investigate the role of the integrin alpha 8-subunit (alpha 8) during lung development. Wild type and alpha 8-deficient lungs were explanted at embryonic days 11.5/12.5. After 24-73 h in culture alpha 8-deficient lung explants displayed reduced growth, reduced branching, enlarged endbuds, altered branching patterns, and faster spontaneous contractions of the airways as compared to wild type. Postnatally, a stereological investigation revealed that lung volume, alveolar surface area, and the length of the free septal edge were significantly reduced in alpha 8-deficient lungs at postnatal days P4 and P7. An increased formation of new septa in alpha 8-deficient lungs rescued the phenotype. At day P90 alpha 8-deficient lungs were comparable to wild type. We conclude that alpha 8 beta 1 takes not only part in the control of branching, but also possesses a morphogenic effect on the pattern and size of the future airways. Furthermore, we conclude that the phenotype observed at day P4 is caused by reduced branching and is rescued by a pronounced formation of the new septa throughout alveolarization. More studies are needed to understand the mechanism responsible for the formation of new septa in the absence of alpha 8 beta 1 in order to be of potential therapeutic benefit for patients suffering from structural lung diseases.
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APA:
Cremona, T.P., Hartner, A., & Schittny, J.C. (2020). The Development of Integrin Alpha-8 Deficient Lungs Shows Reduced and Altered Branching and a Correction of the Phenotype During Alveolarization. Frontiers in Physiology, 11. https://dx.doi.org/10.3389/fphys.2020.530635
MLA:
Cremona, Tiziana P., Andrea Hartner, and Johannes C. Schittny. "The Development of Integrin Alpha-8 Deficient Lungs Shows Reduced and Altered Branching and a Correction of the Phenotype During Alveolarization." Frontiers in Physiology 11 (2020).
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