Transforming growth factor-β in stem cells and tissue homeostasis

TGF-beta 1-3 are unique multi-functional growth factors that are only expressed in mammals, and mainly secreted and stored as a latent complex in the extracellular matrix (ECM). The biological functions of TGF-beta in adults can only be delivered after ligand activation, mostly in response to environmental perturbations. Although involved in multiple biological and pathological processes of the human body, the exact roles of TGF-beta in maintaining stem cells and tissue homeostasis have not been well-documented until recent advances, which delineate their functions in a given context. Our recent findings, along with data reported by others, have clearly shown that temporal and spatial activation of TGF-beta is involved in the recruitment of stem/progenitor cell participation in tissue regeneration/remodeling process, whereas sustained abnormalities in TGF-beta ligand activation, regardless of genetic or environmental origin, will inevitably disrupt the normal physiology and lead to pathobiology of major diseases. Modulation of TGF-beta signaling with different approaches has proven effective pre-clinically in the treatment of multiple pathologies such as sclerosis/fibrosis, tumor metastasis, osteoarthritis, and immune disorders. Thus, further elucidation of the mechanisms by which TGF-beta is activated in different tissues/organs and how targeted cells respond in a context-dependent way can likely be translated with clinical benefits in the management of a broad range of diseases with the involvement of TGF-beta.