Transforming growth factor beta 3 (TGF-β3) is a type of protein, known as a cytokine, which is involved in cell differentiation, embryogenesis and development. It belongs to a large family of cytokines called the Transforming growth factor beta superfamily, which includes the TGF-β family, Bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs), inhibins and activins.[1]
TGF-β3 is believed to regulate molecules involved in cellular adhesion and extracellular matrix (ECM) formation during the process of palate development. Without TGF-β3, mammals develop a deformity known as a cleft palate.[2][3] This is caused by failure of epithelial cells in both sides of the developing palate to fuse. TGF-β3 also plays an essential role in controlling the development of lungs in mammals, by also regulating cell adhesion and ECM formation in this tissue,[4] and controls wound healing by regulating the movements of epidermal and dermal cells in injured skin.[5]
[edit] Clinical research
After successful phase I/II trials,[6] human recombinant TGF-β3 (Avotermin, planned trade name Juvista) failed in Phase III trials.[7]
[edit] References
- ^ Herpin A, Lelong C, Favrel P (2004). "Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans". Dev Comp Immunol 28 (5): 461–85. doi:10.1016/j.dci.2003.09.007. PMID 15062644.
- ^ Taya Y, O'Kane S, Ferguson M (1999). "Pathogenesis of cleft palate in TGF-beta3 knockout mice". Development 126 (17): 3869–79. PMID 10433915.
- ^ Dudas M, Nagy A, Laping N, Moustakas A, Kaartinen V (2004). "Tgf-beta3-induced palatal fusion is mediated by Alk-5/Smad pathway". Dev Biol 266 (1): 96–108. doi:10.1016/j.ydbio.2003.10.007. PMID 14729481.
- ^ Kaartinen V, Voncken J, Shuler C, Warburton D, Bu D, Heisterkamp N, Groffen J (1995). "Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction". Nat Genet 11 (4): 415–21. doi:10.1038/ng1295-415. PMID 7493022.
- ^ Bandyopadhyay B, Fan J, Guan S, Li Y, Chen M, Woodley DT, Li W (2006). "A "traffic control" role for TGFbeta3: orchestrating dermal and epidermal cell motility during wound healing". J Cell Biol. 172 (7): 1093–105. doi:10.1083/jcb.200507111. PMC 2063766. PMID 16549496. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2063766.
- ^ Ferguson, Mark; Duncan, J; Bond, J; Bush, J; Durani, P; So, K; Taylor, L; Chantrey, J et al. (11 April 2009). "Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies". Lancet 373 (9671): 1264–1274. doi:10.1016/S0140-6736(09)60322-6. PMID 19362676. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60322-6/abstract.
- ^ Renovo shares plummet 75% as scar revision product Juvista fails to meet study endpoints, 14 February 2011
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| TGF beta superfamily of ligands |
TGF beta family (TGF-β1, TGF-β2, TGF-β3)
Bone morphogenetic proteins (BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a, BMP8b, BMP10 , BMP15)
Growth differentiation factors (GDF1, GDF2, GDF3, GDF5, GDF6, GDF7, Myostatin/GDF8, GDF9, GDF10, GDF11, GDF15)
Other ( Activin and inhibin, Anti-müllerian hormone, Nodal)
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TGF beta receptors
(Activin, BMP) |
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| Transducers/SMAD |
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| Ligand inhibitors |
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| Coreceptors |
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| Other |
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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| Fibroblast |
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| EGF-like domain |
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| TGFβ pathway |
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| Insulin-like |
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| Platelet-derived |
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| Vascular endothelial |
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| Other |
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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