Expression of the Integrin Subunit α8 in Murine Lung Development

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Abstract
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 α8 associates with the β1-subunit to form an RGD-binding integrin. We previously showed that, in adult lung, α8 is expressed in contractile interstitial cells and smooth muscle cells and is upregulated in lung injury. To gain insight into the function of α8 during lung development, we examined the spatiotemporal expression of α8 throughout murine lung development. We compared the distribution of α8 with α-smooth muscle actin (αSMA), fibronectin (α8 ligand), and cytokeratin. α8 co-localized with αSMA and fibronectin in the peribronchial and perivascular regions. In all stages, α8 immunoreactivity was detected diffusely in the mesenchyme except for cells surrounding distal, newly forming airways. α8, αSMA, and fibronectin co-localized at tips of secondary septae in the alveolar stage. We conclude that α8 is marker for lung mesenchymal cells starting early in development. α8 is also a marker for smooth muscle cells, expressed as early as αSMA. Co-localization of α8 with fibronectin suggests a role in branching morphogenesis. Furthermore, α8 may participate in secondary septation by modulating signals from the extracellular matrix to alveolar myofibroblasts.