TGF-β1 as a therapeutic target for pulmonary fibrosis and COPD

TGF-β1 is a multifunctional molecule that is expressed in an exaggerated fashion during injury, inflammation and repair. Its expression is dysregulated in lung tissues from patients with pulmonary fibrosis and chronic obstructive pulmonary disease. In animal models, introduction of TGF-β1 expression in the lung causes prominent tissue fibrosis and alveolar destruction. On the other hand, the exaggerated production of TGF-β1, an inability to activate TGF-β1 or a block in TGF-β1 signaling have all been associated with the development of emphysematous pulmonary lesions. A number of studies have demonstrated that TGF-β1 is a major player in the pathogenesis of pulmonary fibrosis and emphysema. In this review, we discuss how TGF-β1 expression is regulated and mechanistically related to the development of tissue fibrosis and emphysema in experimental animal models and humans. We further highlight potential therapeutic options that control TGF-β1-associated genes or signals to restore extracellular matrix homeostasis in which TGF-β1 plays a central role.