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Gene Review

Tgfb3  -  transforming growth factor, beta 3

Mus musculus

Synonyms: TGF-beta-3, Tgfb-3, Transforming growth factor beta-3
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Disease relevance of Tgfb3


High impact information on Tgfb3

  • Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction [2].
  • This study demonstrates an essential function for TGF-beta 3 in the normal morphogenesis of palate and lung, and directly implicates this cytokine in mechanisms of epithelial-mesenchymal interaction [2].
  • TGF-beta 1, TGF-beta 2, and TGF-beta 3 are expressed in distinct but overlapping patterns in the developing mouse mammary gland [6].
  • In the present study, we determined to establish the role of TGF-beta2 and TGF-beta3 in mediating apoptosis in non-neuronal tissue by analyzing the intestinal mucosa of Tgfbeta2(+/-) and Tgfbeta3(+/-) heterozygous mice [7].
  • Immunohistochemical localization of TGF beta 1, TGF beta 2, and TGF beta 3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development [8].

Chemical compound and disease context of Tgfb3


Biological context of Tgfb3

  • An alternative interpretation is that the delayed expression of Tgfb2 and Tgfb3 that occurs in the absence of transforming growth factor-beta1 results in the delayed wound healing, suggesting that transforming growth factor-beta2 and/or transforming growth factor-beta3 play important parts in wound healing [12].
  • One was mapped to the central region of mouse chromosome 12 between D12Mit4 and D12Mit5, near fos and Tgfb3 [13].
  • Together, the results clearly demonstrate that TGF-beta2 and TGF-beta3 are essential signals for differentiation of midbrain progenitors toward neuronal fate and dopaminergic phenotype [14].
  • Furthermore, in several organ systems, TGF beta 3 transcripts are expressed during periods of active morphogenesis suggesting that the protein may be an important factor for the growth and differentiation of many embryonic tissues [15].
  • Developing alveolar tissue and its associated ducts displayed striking TGF-beta 3 immunoreactivity which was greatly reduced during lactation [16].

Anatomical context of Tgfb3


Associations of Tgfb3 with chemical compounds

  • Odontoblast-like cells obtained in the presence of IGF-1 combined with heparin did not express TGF beta 1 transcripts and expressed weakly TGF beta 3 transcripts [18].
  • We analyzed the expression pattern of transforming growth factor-beta isoforms (TGF-beta1, TGF-beta2 and TGF-beta3) in the developing brain of embryos derived from the normal and diabetic mice exposed to cyclophosphamide (CP), a cytotoxic teratogen [19].
  • The increases in mRNA steady-state levels for TGF-beta 2 and TGF-beta 3, as for TGF-beta 1, were rapid and transient in nature, again arguing for direct mediation by RA [20].
  • Exposure of early neural plate stage embryos to retinoic acid caused reduced expression of TGF beta 1 and TGF beta 2 proteins but had no effect on TGF beta 3 [21].
  • In comparison, neither an injection of E2 nor one of P4 exerted significant effects on TGF beta 3 mRNA levels.(ABSTRACT TRUNCATED AT 400 WORDS)[22]

Regulatory relationships of Tgfb3


Other interactions of Tgfb3

  • GDF5, TGF-beta2, and TGF-beta3 showed maximal expression on day 7, when type II collagen expression peaked during cartilage formation [26].
  • Coimmunoprecipitations demonstrated interaction between P311 and TGF-beta1 and 2, but not TGF-beta3 [27].
  • In TGF-beta3 null mice, Pax9 expression was much reduced in the palatal medial edge at the critical time of palatal fusion (E14.5-E15.5) [1].
  • TGF-beta2 null mice exhibit a broad range of developmental defects, including cardiac, lung, craniofacial, limb, eye, ear and urogenital defects, whereas TGF-beta3 gene ablation results exclusively in defective palatogenesis and delayed pulmonary development [28].
  • Targeted disruption of both TGF-beta2 and TGF-beta3 genes results in perinatal lethality [28].

Analytical, diagnostic and therapeutic context of Tgfb3

  • Whole mount in situ hybridization was conducted with use of Pax9 and Shh riboprobes for TGF-beta3 null, heterozygous and wild type mice at E12.5-E16 [1].
  • METHODS: Intestinal localization of TGF-beta2 and TGF-beta3 isoforms and antiapoptotic molecules Bcl-xL and Bcl-2 was examined immunocytochemically and by Western blot analysis [7].
  • Based on this pharmacokinetic data, we next administered neutralizing antibodies to TGF-beta1 and -beta2 or exogenous TGF-beta3 peptide by local application and intraperitoneal injection at various times before and after surgery [29].
  • The remaining activity in CM correlates with high expression of TGF-beta 3 by Northern blot analysis in these cells [30].
  • Prevention of mature TGF-beta 3 activity during a specific time window of development in palate organ cultures, either by antisense oligodeoxynucleotides or neutralizing antibody, resulted in failure of palate fusion [31].


  1. Temporal and spatial expression of Pax9 and Sonic hedgehog during development of normal mouse palates and cleft palates in TGF-beta3 null embryos. Sasaki, Y., O'kane, S., Dixon, J., Dixon, M.J., Ferguson, M.W. Arch. Oral Biol. (2007) [Pubmed]
  2. Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction. Kaartinen, V., Voncken, J.W., Shuler, C., Warburton, D., Bu, D., Heisterkamp, N., Groffen, J. Nat. Genet. (1995) [Pubmed]
  3. Transforming growth factors-beta 1, -beta 2, and -beta 3 stimulate fibroblast procollagen production in vitro but are differentially expressed during bleomycin-induced lung fibrosis. Coker, R.K., Laurent, G.J., Shahzeidi, S., Lympany, P.A., du Bois, R.M., Jeffery, P.K., McAnulty, R.J. Am. J. Pathol. (1997) [Pubmed]
  4. Elevated transforming growth factor-beta 1 and beta 3 mRNA levels are associated with ras + myc-induced carcinomas in reconstituted mouse prostate: evidence for a paracrine role during progression. Merz, V.W., Miller, G.J., Krebs, T., Timme, T.L., Kadmon, D., Park, S.H., Egawa, S., Scardino, P.T., Thompson, T.C. Mol. Endocrinol. (1991) [Pubmed]
  5. TGF-beta 3 decreases type I collagen and scarring after labioplasty. Hosokawa, R., Nonaka, K., Morifuji, M., Shum, L., Ohishi, M. J. Dent. Res. (2003) [Pubmed]
  6. Inhibition of mammary duct development but not alveolar outgrowth during pregnancy in transgenic mice expressing active TGF-beta 1. Pierce, D.F., Johnson, M.D., Matsui, Y., Robinson, S.D., Gold, L.I., Purchio, A.F., Daniel, C.W., Hogan, B.L., Moses, H.L. Genes Dev. (1993) [Pubmed]
  7. The role of transforming growth factor beta-2, beta-3 in mediating apoptosis in the murine intestinal mucosa. Dünker, N., Schmitt, K., Schuster, N., Krieglstein, K. Gastroenterology (2002) [Pubmed]
  8. Immunohistochemical localization of TGF beta 1, TGF beta 2, and TGF beta 3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development. Pelton, R.W., Saxena, B., Jones, M., Moses, H.L., Gold, L.I. J. Cell Biol. (1991) [Pubmed]
  9. All-trans retinoic acid inhibited chondrogenesis of mouse embryonic palate mesenchymal cells by down-regulation of TGF-beta/Smad signaling. Yu, Z., Xing, Y. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  10. Opposing roles for TGF-beta1 and TGF-beta3 isoforms in experimental autoimmune encephalomyelitis. Matejuk, A., Dwyer, J., Hopke, C., Vandenbark, A.A., Offner, H. Cytokine (2004) [Pubmed]
  11. Effect of ormeloxifene on ovariectomy-induced bone resorption, osteoclast differentiation and apoptosis and TGF beta-3 expression. Narayana Murthy, P.S., Sengupta, S., Sharma, S., Singh, M.M. J. Steroid Biochem. Mol. Biol. (2006) [Pubmed]
  12. Delayed wound healing in immunodeficient TGF-beta 1 knockout mice. Crowe, M.J., Doetschman, T., Greenhalgh, D.G. J. Invest. Dermatol. (2000) [Pubmed]
  13. The mouse glutathione peroxidase Gpx2 gene maps to chromosome 12; its pseudogene Gpx2-ps maps to chromosome 7. Chu, F.F., Esworthy, R.S., Burmeister, M. Genomics (1996) [Pubmed]
  14. Transforming growth factor beta is required for differentiation of mouse mesencephalic progenitors into dopaminergic neurons in vitro and in vivo: ectopic induction in dorsal mesencephalon. Roussa, E., Wiehle, M., Dünker, N., Becker-Katins, S., Oehlke, O., Krieglstein, K. Stem Cells (2006) [Pubmed]
  15. In situ hybridization analysis of TGF beta 3 RNA expression during mouse development: comparative studies with TGF beta 1 and beta 2. Pelton, R.W., Dickinson, M.E., Moses, H.L., Hogan, B.L. Development (1990) [Pubmed]
  16. Regulated expression and growth inhibitory effects of transforming growth factor-beta isoforms in mouse mammary gland development. Robinson, S.D., Silberstein, G.B., Roberts, A.B., Flanders, K.C., Daniel, C.W. Development (1991) [Pubmed]
  17. Pathogenesis of cleft palate in TGF-beta3 knockout mice. Taya, Y., O'Kane, S., Ferguson, M.W. Development (1999) [Pubmed]
  18. Comparative analysis of TGF beta s, BMPs, IGF1, msxs, fibronectin, osteonectin and bone sialoprotein gene expression during normal and in vitro-induced odontoblast differentiation. Bègue-Kirn, C., Smith, A.J., Loriot, M., Kupferle, C., Ruch, J.V., Lesot, H. Int. J. Dev. Biol. (1994) [Pubmed]
  19. Enhanced expression of transforming growth factor-beta isoforms in the neural tube of embryos derived from diabetic mice exposed to cyclophosphamide. Lian, Q., Samuel, T.S., Dheen, S.T. Neurosci. Lett. (2003) [Pubmed]
  20. Role of TGF-beta in RA-induced cleft palate in CD-1 mice. Degitz, S.J., Morris, D., Foley, G.L., Francis, B.M. Teratology (1998) [Pubmed]
  21. Interactions between retinoids and TGF beta s in mouse morphogenesis. Mahmood, R., Flanders, K.C., Morriss-Kay, G.M. Development (1992) [Pubmed]
  22. Expression of transforming growth factor-beta isoforms (beta 2 and beta 3) in the mouse uterus: analysis of the periimplantation period and effects of ovarian steroids. Das, S.K., Flanders, K.C., Andrews, G.K., Dey, S.K. Endocrinology (1992) [Pubmed]
  23. Transforming growth factor-beta stimulates vascular endothelial growth factor production by folliculostellate pituitary cells. Renner, U., Lohrer, P., Schaaf, L., Feirer, M., Schmitt, K., Onofri, C., Arzt, E., Stalla, G.K. Endocrinology (2002) [Pubmed]
  24. Antisense oligonucleotides to CRABP I and II alter the expression of TGF-beta 3, RAR-beta, and tenascin in primary cultures of embryonic palate cells. Nugent, P., Greene, R.M. In Vitro Cell. Dev. Biol. Anim. (1995) [Pubmed]
  25. TGF-beta3 regulates anchoring junction dynamics in the seminiferous epithelium of the rat testis via the Ras/ERK signaling pathway: An in vivo study. Xia, W., Cheng, C.Y. Dev. Biol. (2005) [Pubmed]
  26. Differential temporal expression of members of the transforming growth factor beta superfamily during murine fracture healing. Cho, T.J., Gerstenfeld, L.C., Einhorn, T.A. J. Bone Miner. Res. (2002) [Pubmed]
  27. P311 binds to the latency associated protein and downregulates the expression of TGF-beta1 and TGF-beta2. Paliwal, S., Shi, J., Dhru, U., Zhou, Y., Schuger, L. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  28. Targeted mutations of transforming growth factor-beta genes reveal important roles in mouse development and adult homeostasis. Dünker, N., Krieglstein, K. Eur. J. Biochem. (2000) [Pubmed]
  29. Experimental manipulation of transforming growth factor-beta isoforms significantly affects adhesion formation in a murine surgical model. Gorvy, D.A., Herrick, S.E., Shah, M., Ferguson, M.W. Am. J. Pathol. (2005) [Pubmed]
  30. Secretion of transforming growth factor-beta isoforms by embryonic stem cells: isoform and latency are dependent on direction of differentiation. Slager, H.G., Freund, E., Buiting, A.M., Feijen, A., Mummery, C.L. J. Cell. Physiol. (1993) [Pubmed]
  31. Inhibition of TGF-beta 3 (but not TGF-beta 1 or TGF-beta 2) activity prevents normal mouse embryonic palate fusion. Brunet, C.L., Sharpe, P.M., Ferguson, M.W. Int. J. Dev. Biol. (1995) [Pubmed]
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