Factor de crecemento transformante beta 3

O factor de crecemento transformante beta 3 (TGF-β3) é unha proteína que nos humanos está codificado polo xene TGFB3 do cromosoma 14.^[1][2]

Representación do TG-β3 baseada en PDB 1ktz
Identificadores
Símbolo	TGFB3
Símbolos alt.	ARVD; ARVD1; RNHF; TGF-beta3
Entrez	7043
OMIM	190230
RefSeq	NP_003230
UniProt	P10600
Outros datos
Locus	Cr. 14 :(75.96 – 75.98 Mb)

É unha proteína que funciona como citocina, que está implicada na diferenciación celular, embrioxénese e desenvolvemento. Pertence a unha gran familia de citocinas chamada superfamilia do TGF-β, que inclúe a familia do TGF-β, as proteínas morfoxénicas óseas (BMPs), factores de diferenciación e crecemento (GDFs), inhibinas e activinas.^[3]

O TGF-β3 crese que regula moléculas implicadas na adhesión celular e formación da matriz extracelular durante o proceso do desenvolvemento do padal. Sen TGF-β3, os mamíferos desenvolven unha deformidade denominada padal fendido ou labio leporino.^[4][5] Isto é causado pola incapacidade das células epiteliais en ambos os lados do corpo de desenvolver un padal fusionado. O TGF-β3 tamén xoga un papel esencial no control no desenvolvemento dos pulmóns en mamíferos, pero tamén regula a adhesión celular e a formación da matriz extracelular neste tecido,^[6] e controla a curación ao regular os movementos das células epidérmicas e dérmicas na pel lesionada.^[1]

Interaccións

O TGF-β3 ten interaccións co receptor de TGF-β 2.^{[7][8][9][10]}

Investigación clínica

Realizáronse con éxito ensaios clínicos en fases I e II,^[11] co TGF-β3 recombinante humano (Avotermin, co nome comercial previsto Juvista), pero fracasou nos ensaios en fase III.^[12]

Notas

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. PMC 2063766. PMID 16549496. doi:10.1083/jcb.200507111.
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. PMID 15062644. doi:10.1016/j.dci.2003.09.007.
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. PMID 14729481. doi:10.1016/j.ydbio.2003.10.007.
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. PMID 7493022. doi:10.1038/ng1295-415.
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. PMID 12729750. doi:10.1016/S0022-2836(03)00360-7.
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. PMID 11850637. doi:10.1038/nsb766.
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. PMID 9872992. doi:10.1074/jbc.274.2.584.
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. PMC 133482. PMID 11157754. doi:10.1093/emboj/20.3.480.
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. PMID 19362676. doi:10.1016/S0140-6736(09)60322-6.
12. Renovo shares plummet 75% as scar revision product Juvista fails to meet study endpoints, 14 February 2011

Véxase tamén

Outros artigos

• Factor de crecemento transformante beta

Ligazóns externas

• GeneReviews/NCBI/NIH/UW entry on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant
• OMIM entries on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant

Bibliografía

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