Transforming growth factor-β superfamily in obstructive lung diseases. more suspects than TGF-β alone

Asthma and chronic obstructive pulmonary disease are respiratory disorders and a major global health problem with increasing incidence and severity. Genes originally associated with lung development could be relevant in the pathogenesis of chronic obstructive pulmonary disease/asthma, owing to either an early-life origin of adult complex diseases or their dysregulation in adulthood upon exposure to environmental stressors (e.g., smoking). The transforming growth factor (TGF)-β superfamily is conserved through evolution and is involved in a range of biological processes, both during development and in adult tissue homeostasis. TGF-β1 has emerged as an important regulator of lung and immune system development. However, considerable evidence has been presented for a role of many of the other ligands of the TGF-β superfamily in lung pathology, including activins, bone morphogenetic proteins, and growth differentiation factors. In this review, we summarize the current knowledge on the mechanisms by which activin, bone morphogenetic protein, and growth differentiation factor signaling contribute to the pathogenesis of obstructive airway diseases.