Abstract

Alveolarization occurs after branching morphogenesis has laid down the conducting airways and is morphologically characterized by the eruption and elongation of secondary septa from the primary saccules. Secondary septa contain a central connective tissue core that is formed by fibroblasts or pericytes and supports alveolar epithelial and endothelial cells, which are separated by a thin basement membrane. Epithelial cells arise from precursors, located at the termini of branching airways, which give rise to alveolar type 2 (AT2) and Clara cells, or eventually alveolar type 1 (AT1) cells. AT2 cells either differentiate into AT1 cells, which form a flattened but expansive barrier mediating the exchange of gasses and liquids, or alternatively retain their characteristic production of surfactant lipids and proteins. Some septal fibroblasts express platelet-derived growth factor (PDGF)-receptor alpha (PDGFRα), which influences the proliferation and differentiation of these cells into lipid-storage or myofibroblast phenotypes. Alveolar myofibroblasts produce the elastic fiber, which not only mechanically supports the septa, but also regulates the activities of regulatory polypeptides such as transforming growth factor-β, fibroblast growth factors, and PDGF. The new insights, summarized in this chapter, bring us closer to developing strategies for promoting effective alveolarization in pre-mature infants and possibly regenerating damaged alveoli in adults.

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