2016 | Masato Morikawa, Rik Derynck, and Kohei Miyazono
The TGF-β family is a group of growth and differentiation factors with complex names and diverse biological activities. It consists of 33 genes in mammals, encoding homo- and heterodimers. TGF-β is the best-studied member of this family, playing key roles in cell proliferation, differentiation, wound healing, and immune system regulation. Initially thought to stimulate cell proliferation, TGF-β is now recognized as a bifunctional regulator that can either inhibit or stimulate cell growth, depending on the cellular context. TGF-β was first identified as a cytokine that induces cellular transformation and anchorage-independent growth, but later found to also act as a growth inhibitor. Its dual roles in various biological processes have been well documented, with TGF-β signaling being crucial for normal development and physiology, and its dysregulation implicated in diseases such as connective tissue disorders, fibrosis, and cancer.
The TGF-β family includes several subfamilies, such as the TGF-β isoforms, activins, nodal, bone morphogenetic proteins (BMPs), and growth and differentiation factors (GDFs). These proteins are encoded by 33 genes in mammals and are characterized by their structural and functional diversity. The TGF-β family members are typically secreted as latent complexes, which are activated upon specific interactions with integrins and other proteins. The activation of TGF-β is tightly regulated, and its signaling pathways involve the Smad proteins, which mediate intracellular signaling. TGF-β signaling also interacts with other pathways, such as PI3K-Akt and MAP kinase, to regulate various cellular processes.
The TGF-β family plays essential roles in cell proliferation, differentiation, and tissue homeostasis. It controls the development and function of diverse cell types, including mesenchymal cells, stem cells, and immune cells. TGF-β signaling is also involved in wound healing, where it promotes ECM deposition and tissue remodeling. In the immune system, TGF-β acts as an immunosuppressive cytokine, inhibiting T-cell proliferation and promoting the differentiation of regulatory T cells. However, TGF-β can also promote the development of proinflammatory T helper cells, depending on the presence of other cytokines.
Dysregulation of TGF-β signaling is implicated in various diseases, including connective tissue disorders, fibrosis, and cancer. Mutations in genes encoding TGF-β family members can lead to abnormal activation of TGF-β, contributing to the pathogenesis of these diseases. The complex roles of TGF-β in different biological contexts highlight the importance of understanding its signaling pathways and regulatory mechanisms for developing therapeutic strategies.The TGF-β family is a group of growth and differentiation factors with complex names and diverse biological activities. It consists of 33 genes in mammals, encoding homo- and heterodimers. TGF-β is the best-studied member of this family, playing key roles in cell proliferation, differentiation, wound healing, and immune system regulation. Initially thought to stimulate cell proliferation, TGF-β is now recognized as a bifunctional regulator that can either inhibit or stimulate cell growth, depending on the cellular context. TGF-β was first identified as a cytokine that induces cellular transformation and anchorage-independent growth, but later found to also act as a growth inhibitor. Its dual roles in various biological processes have been well documented, with TGF-β signaling being crucial for normal development and physiology, and its dysregulation implicated in diseases such as connective tissue disorders, fibrosis, and cancer.
The TGF-β family includes several subfamilies, such as the TGF-β isoforms, activins, nodal, bone morphogenetic proteins (BMPs), and growth and differentiation factors (GDFs). These proteins are encoded by 33 genes in mammals and are characterized by their structural and functional diversity. The TGF-β family members are typically secreted as latent complexes, which are activated upon specific interactions with integrins and other proteins. The activation of TGF-β is tightly regulated, and its signaling pathways involve the Smad proteins, which mediate intracellular signaling. TGF-β signaling also interacts with other pathways, such as PI3K-Akt and MAP kinase, to regulate various cellular processes.
The TGF-β family plays essential roles in cell proliferation, differentiation, and tissue homeostasis. It controls the development and function of diverse cell types, including mesenchymal cells, stem cells, and immune cells. TGF-β signaling is also involved in wound healing, where it promotes ECM deposition and tissue remodeling. In the immune system, TGF-β acts as an immunosuppressive cytokine, inhibiting T-cell proliferation and promoting the differentiation of regulatory T cells. However, TGF-β can also promote the development of proinflammatory T helper cells, depending on the presence of other cytokines.
Dysregulation of TGF-β signaling is implicated in various diseases, including connective tissue disorders, fibrosis, and cancer. Mutations in genes encoding TGF-β family members can lead to abnormal activation of TGF-β, contributing to the pathogenesis of these diseases. The complex roles of TGF-β in different biological contexts highlight the importance of understanding its signaling pathways and regulatory mechanisms for developing therapeutic strategies.