Heparin inhibits lung branching morphogenesis: potential role of smooth muscle cells in cleft formation.

Lung branching morphogenesis is the process by which the embryonic lung undergoes repetitive branching to form the bronchial tree. This process occurs during the pseudoglandular stage of lung development and requires epithelial-mesenchymal interactions. Coinciding with lung branching morphogenesis is the appearance of parabronchial smooth muscle cells (PSMCs) and the accumulation of extracellular matrices (ECMs) around the developing airways. The authors previously reported in preliminary form that heparin prevents the branching of murine lung explants (Roman et al., Am Rev Respir Dis. 1991; 143:A401); this article corroborates those early observations and expands them by demonstrating that heparin results in disruption of PSMC distribution and abnormal organization of ECMs around the developing airways. These changes were associated with inhibition of lung branching morphogenesis in the absence of effects on cell proliferation. The data provide further support for the role of ECMs in lung branching morphogenesis, and points to PSMCs as potential players in this process.