Transforming Growth Factor-beta
Title: Transforming Growth Factor-b
Additional Names: TGF-b
Literature References: Family of multifunctional cytokines that regulate cellular differentiation, motility and growth. Also regulate the synthesis and deposition of the extracellular matrix. Involved in various physiological processes including embryogenesis, immunoregulation, bone remodeling and wound healing. Secreted by virtually all cell types as a biologically inactive (latent) form which is stored at the cell surface and in the extracellular matrix. The mature, active cytokine is a homodimer; mol wt 25 kDa. At least 5 isoforms have been identified. The three mammalian isoforms (TGF-b1, b2, and b3) exhibit 70-80% sequence homology, bind to the same receptors and exert similar biological effects. TGF-b1 is the most abundant. Biological effects are mediated by binding to membrane receptors that exist on virtually all cells. Released from degranulating platelets at the site of a wound, TGF-b initiates angiogenesis and collagen synthesis. Acts as a chemoattractant and activator of macrophages and fibroblasts. Dysregulation is implicated in the pathogenesis of fibrotic diseases. Inhibits the growth of most epithelial and lymphoid cells. Escape from this normal control mechanism is implicated in carcinogenic transformation. Initial description: J. E. DeLarco, G. J. Todaro, Proc. Natl. Acad. Sci. USA 75, 4001 (1978). Crystal structure of TGF-b2: S. Daopin et al., Science 257, 369 (1992). Review of physiological actions: A. B. Roberts, M. B. Sporn, Growth Factors 8, 1-9 (1993); of latent forms, binding proteins and receptors: K. Miyazono et al., ibid., 11-22. Proposed mechanisms for tumor cell transformation: M. J. Newman, Cancer Metastasis Rev. 12, 239-254 (1993). Role in embryogenesis: N. L. McCartney-Francis, S. M. Wahl, J. Leukocyte Biol. 55, 401-409 (1994); in tissue fibrosis: W. A. Border, N. A. Noble, N. Engl. J. Med. 331, 1286-1292 (1994); in kidney disease: K. Sharma, F. N. Ziyadeh, Am. J. Physiol. 266, F829-F842 (1994). Review of potential clinical applications in oncology: J. Kekow, G. J. Wiedemann, Int. J. Oncol. 7, 177-182 (1995).

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