Expression of the integrin subunit α8 in murine lung development

The complex interplay between cells and extracellular matrix (ECM) proteins is critical for lung development. Integrins are key modulators of this interaction. The integrin subunit alpha8 associates with the beta(1)-subunit to form an RGD-binding integrin. We previously showed that, in adult lung, alpha8 is expressed in contractile interstitial cells and smooth muscle cells and is upregulated in lung injury. To gain insight into the function of alpha8 during lung development, we examined the spatiotemporal expression of alpha8 throughout murine lung development. We compared the distribution of alpha8 with alpha-smooth muscle actin (alphaSMA), fibronectin (alpha8 ligand), and cytokeratin. alpha8 co-localized with alphaSMA and fibronectin in the peribronchial and perivascular regions. In all stages, alpha8 immunoreactivity was detected diffusely in the mesenchyme except for cells surrounding distal, newly forming airways. alpha8, alphaSMA, and fibronectin co-localized at tips of secondary septae in the alveolar stage. We conclude that alpha8 is marker for lung mesenchymal cells starting early in development. alpha8 is also a marker for smooth muscle cells, expressed as early as alphaSMA. Co-localization of alpha8 with fibronectin suggests a role in branching morphogenesis. Furthermore, alpha8 may participate in secondary septation by modulating signals from the extracellular matrix to alveolar myofibroblasts.