Transforming growth factor-beta in tissue fibrosis

TGF-beta is extensively implicated in the pathogenesis of fibrosis. In fibrotic lesions, spatially restricted generation of bioactive TGF-beta from latent stores requires the cooperation of proteases, integrins, and specialized extracellular matrix molecules. Although fibroblasts are major targets of TGF-beta, some fibrogenic actions may reflect activation of other cell types, including macrophages, epithelial cells, and vascular cells. TGF-beta-driven fibrosis is mediated through Smad-dependent or non-Smad pathways and is modulated by coreceptors and by interacting networks. This review discusses the role of TGF-beta in fibrosis, highlighting mechanisms of TGF-beta activation and signaling, the cellular targets of TGF-beta actions, and the challenges of therapeutic translation.