LSC Abstract – Alpha8 integrin deficiency alters branching morphogenesis and alveolarization during mouse lung development

Abstract

RATIONALE: During pre and postnatal lung development, an intensive epithelial-mesenchymal interaction occurs and integrins represent one of the key elements. These extracellular matrix receptors form cell membrane hetero-dimers of an alpha and a beta subunit. The integrin alpha8 subunit (α8) exclusively dimerizes with the beta1 subunit (β1) and forms a cellular receptor for fibronectin, vitronectin, osteopontin, nephronectin, and tenascin-C. α8β1 is highly expressed in several mouse tissues including lung and kidney. AIM: We investigate how α8deficiency influences branching morphogenesis and alveolarization. METHODS: Wild type and α8-deficient fetal lung were explanted and cultured. Organ cultures and lung morphology was assessed from embryonic day E11.5 to postnatal day P90. RESULTS: At embryonic stage, 71% of the α8-deficient lung explants displayed reduced branching, enlarged endbuds, and altered branching pattern compared to wild type explants. Postnatally, a stereological investigation revealed that lung volume, alveolar surface area, and the length of the free septal edge were significantly reduce inα8-deficient lungs at postnatal day P4. Interestingly, at P90 α8-deficient lungs were comparable to WT lungs because of a tremendous new septa formation. CONCLUSIONS: α8β1 takes not only part in the control of branching, but also possesses an additional morphogenic effect on the pattern and size of the branches. Furthermore, α8β1 plays a role during alveolarization and in the postnatal rescue mechanism responsible for the pronounce formation of new septa. This abstract has been presented previously at the European Respiratory Society9s Lung Science Conference in March 2016.