[HTML][HTML] Mesenchymal regulation of alveolar repair in pulmonary fibrosis

KC Fang - American journal of respiratory cell and molecular …, 2000 - atsjournals.org
KC Fang
American journal of respiratory cell and molecular biology, 2000atsjournals.org
Induction of alveolar epithelial cell phenotypes via mesenchymal signaling regulates
pneumocyte differentiation not only during lung development (1, 2) but also during the
response to a myriad of injuries inciting fibrogenesis (3). Signals generated in the epithelium
and the mesenchyme regulate critical functions of cells in both compartments reciprocally,
with transduction mediated by soluble growth factors, membrane-anchored receptors, and
extracellular matrix proteins (4). Such epithelial–mesenchymal interactions characterize …
Induction of alveolar epithelial cell phenotypes via mesenchymal signaling regulates pneumocyte differentiation not only during lung development (1, 2) but also during the response to a myriad of injuries inciting fibrogenesis (3). Signals generated in the epithelium and the mesenchyme regulate critical functions of cells in both compartments reciprocally, with transduction mediated by soluble growth factors, membrane-anchored receptors, and extracellular matrix proteins (4). Such epithelial–mesenchymal interactions characterize remodeling in a variety of tissues, including airways and lung parenchyma (3, 5, 6). Transition from injury to the repair phase in alveolar remodeling requires epithelialization to regenerate pneumocyte populations and the epithelial component of the alveolar barrier. Ordered layering of type I and type II pneumocytes, basement membranes, and capillary endothelial cells establishes compartmentalization that normalizes communication among cells and extracellular matrix components in distinct epithelial and mesenchymal layers. Restoration of alveolar quiescence reverses ventilation–perfusion defects to equilibrate gas exchange. By contrast, unrelenting signaling between the compartments leads to continued invasion of fibroblasts and excessive deposition of matrix proteins, causing intra-alveolar fibrosis and the loss of surface area, which defines the pathophysiology of pulmonary fibrosis (3).
Epithelial cells differentiate into subpopulations, which reconstruct a protective barrier and regulate clearance of alveolar exudates. Type II cells differentiate from cuboidal progenitor cells at septal intersections into thin type I cells that line approximately 90% of the alveolar unit. Subpopulations of type II pneumocytes synthesize surfactants needed to reduce alveolar surface tension and also produce matrix constituents such as fibronectin, collagen IV, and proteoglycan, essential for remodeling. Other type II cells help resorb proteinaceous exudates by releasing fibrinolytic proteases or by upregulating expression of water and ion channels. Some type II pneumocytes also serve
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