Transforming growth factor, beta 3

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External IDsGeneCards: [1]
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SpeciesHumanMouse
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Transforming growth factor beta-3 is a protein that in humans is encoded by the TGFB3 gene.[1][2]

It 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.[3]

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.[4][5] 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,[6] and controls wound healing by regulating the movements of epidermal and dermal cells in injured skin.[1]

Interactions

Transforming growth factor, beta 3 has been shown to interact with TGF beta receptor 2.[7][8][9][10]

Clinical research

After successful phase I/II trials,[11] human recombinant TGF-β3 (Avotermin, planned trade name Juvista) failed in Phase III trials.[12]

References

  1. 1.0 1.1 Bandyopadhyay B, Fan J, Guan S, Li Y, Chen M, Woodley DT, Li W (Mar 2006). "A "traffic control" role for TGFbeta3: orchestrating dermal and epidermal cell motility during wound healing". The Journal of Cell Biology. 172 (7): 1093–105. doi:10.1083/jcb.200507111. PMC 2063766. PMID 16549496.
  2. "Entrez Gene: TGFB3 transforming growth factor, beta 3".
  3. Herpin A, Lelong C, Favrel P (May 2004). "Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans". Developmental and Comparative Immunology. 28 (5): 461–85. doi:10.1016/j.dci.2003.09.007. PMID 15062644.
  4. Taya Y, O'Kane S, Ferguson MW (Sep 1999). "Pathogenesis of cleft palate in TGF-beta3 knockout mice". Development. 126 (17): 3869–79. PMID 10433915.
  5. Dudas M, Nagy A, Laping NJ, Moustakas A, Kaartinen V (Feb 2004). "Tgf-beta3-induced palatal fusion is mediated by Alk-5/Smad pathway". Developmental Biology. 266 (1): 96–108. doi:10.1016/j.ydbio.2003.10.007. PMID 14729481.
  6. Kaartinen V, Voncken JW, Shuler C, Warburton D, Bu D, Heisterkamp N, Groffen J (Dec 1995). "Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction". Nature Genetics. 11 (4): 415–21. doi:10.1038/ng1295-415. PMID 7493022.
  7. De Crescenzo G, Pham PL, Durocher Y, O'Connor-McCourt MD (May 2003). "Transforming growth factor-beta (TGF-beta) binding to the extracellular domain of the type II TGF-beta receptor: receptor capture on a biosensor surface using a new coiled-coil capture system demonstrates that avidity contributes significantly to high affinity binding". Journal of Molecular Biology. 328 (5): 1173–83. doi:10.1016/S0022-2836(03)00360-7. PMID 12729750.
  8. Hart PJ, Deep S, Taylor AB, Shu Z, Hinck CS, Hinck AP (Mar 2002). "Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex". Nature Structural Biology. 9 (3): 203–8. doi:10.1038/nsb766. PMID 11850637.
  9. Barbara NP, Wrana JL, Letarte M (Jan 1999). "Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily". The Journal of Biological Chemistry. 274 (2): 584–94. doi:10.1074/jbc.274.2.584. PMID 9872992.
  10. Rotzer D, Roth M, Lutz M, Lindemann D, Sebald W, Knaus P (Feb 2001). "Type III TGF-beta receptor-independent signalling of TGF-beta2 via TbetaRII-B, an alternatively spliced TGF-beta type II receptor". The EMBO Journal. 20 (3): 480–90. doi:10.1093/emboj/20.3.480. PMC 133482. PMID 11157754.
  11. Ferguson MW, Duncan J, Bond J, Bush J, Durani P, So K, Taylor L, Chantrey J, Mason T, James G, Laverty H, Occleston NL, Sattar A, Ludlow A, O'Kane S (Apr 2009). "Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies". Lancet. 373 (9671): 1264–74. doi:10.1016/S0140-6736(09)60322-6. PMID 19362676.
  12. Renovo shares plummet 75% as scar revision product Juvista fails to meet study endpoints, 14 February 2011

Further reading

External links


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