Transforming growth factor-beta signaling across ages: from distorted lung development to chronic obstructive pulmonary disease

Proceedings of the American Thoracic Society
Rory E MortyOliver Eickelberg

Abstract

The transforming growth factor (TGF)-beta superfamily of secreted growth factors consists of more than 40 members, including the TGF-beta isoforms themselves, bone morphogenetic proteins, and activins. Most of these factors have been shown to be essential for proper organ development, a process often recapitulated in chronic diseases. Importantly, TGF-beta superfamily members are key regulators of extracellular matrix composition and alveolar epithelial cell and fibroblast function in the lung. Both during lung development and disease, TGF-betas therefore control lung homeostasis by providing the structural requirements and functional micromilieu needed for physiological epithelial cell function and proper gas exchange. Prolonged alterations of TGF-beta signaling have been shown to result in structural changes in the lung that compromise gas exchange and lung function, as seen in arrested lung development, a feature of bronchopulmonary dysplasia, lung fibrosis, and chronic obstructive pulmonary disease. All these syndromes share a loss of functional alveolar structures, which ultimately leads to a decreased life expectancy. In this review, we cover our current understanding of the impact of TGF-beta signaling on chronic lung di...Continue Reading

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