Laminins in lung development.

Laminins are essential components of basement membranes, playing important roles in cell adhesion, proliferation, and differentiation. These heterotrimeric glycoproteins are composed of an alpha, beta, and gamma chains held together by disulfide bonds. The first laminin identified, from the mouse Engelbreth-Holm-Swarm (EHS) tumor, is now referred to as laminin-1. Laminin-1 is expressed in the mouse developing lung by epithelial and mesenchymal cells and plays a role in branching morphogenesis. Since laminins are multidomain proteins, different laminin sites are engaged in promoting lung organogenesis by serving different functions at different stages of development. This study shows that the cross region of the molecule selectively promotes epithelial cell proliferation. The outer globular region of alpha 1 and beta 1 chains mediates laminin polymerization and thereby basement membrane formation and epithelial cell polarization. The inner globular region of laminin beta 1 chain binds to heparan sulfate proteoglycan and both stimulate lumen formation. While the combined effect of these laminin active sites results in normal lung tissue structure and branching morphogenesis, different developmental abnormalities of the lung may result from alterations in each of them.