The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Tgfb1  -  transforming growth factor, beta 1

Mus musculus

Synonyms: TGF-beta 1, TGF-beta-1, TGF-beta1, TGFbeta1, Tgfb, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Tgfb1


Psychiatry related information on Tgfb1


High impact information on Tgfb1

  • RORgammat induces transcription of the genes encoding IL-17 and the related cytokine IL-17F in naïve CD4(+) T helper cells and is required for their expression in response to IL-6 and TGF-beta, the cytokines known to induce IL-17 [14].
  • Ubiquitin-mediated degradation a mechanism for fine-tuning TGF-beta signaling [15].
  • Runx3/Pebp2alphaC null mouse gastric mucosa exhibits hyperplasias due to stimulated proliferation and suppressed apoptosis in epithelial cells, and the cells are resistant to growth-inhibitory and apoptosis-inducing action of TGF-beta, indicating that Runx3 is a major growth regulator of gastric epithelial cells [16].
  • Growth/differentiation factor-1 (Gdf-1, encoded by Gdf1) is a TGF-beta family member of unknown function that was originally isolated from an early mouse embryo cDNA library and is expressed specifically in the nervous systemin late-stage embryos and adult mice [17].
  • The transforming growth factor-beta (TGF-beta) superfamily encompasses a large group of structurally related polypeptides that are capable of regulating cell growth and differentiation in a wide range of embryonic and adult tissues [17].

Chemical compound and disease context of Tgfb1


Biological context of Tgfb1


Anatomical context of Tgfb1

  • Together, these results demonstrate that the ex vivo proliferative hyporesponsiveness of Tgfb1(-/-) splenic lymphocytes is due to prior in vivo activation of T cells resulting from deregulated intracellular Ca(2+) levels [27].
  • Here we demonstrate that unlike wild-type splenic lymphocytes, those from Tgfb1(-/-) mice are hyporesponsive to receptor-mediated mitogenic stimulation, as evidenced by diminished proliferation and reduced IL-2 production [27].
  • We show that this effect is the result of an increase in TGF-beta1 and enhanced dermal fibroblast infiltration into wounds of beta(3)-null mice [26].
  • Transgenic mice were generated using a keratin 10 (K10) gene promoter to drive constitutive expression of TGF-beta 1 in the suprabasal keratinocyte compartment [28].
  • Transforming growth factor-beta (TGF-beta) is a potent inhibitor of skeletal muscle differentiation, but the molecular mechanism and signaling events that lead to this inhibition are poorly characterized [29].

Associations of Tgfb1 with chemical compounds

  • A suboptimal concentration of ionomycin in the presence of PMA fully activates Tgfb1(-/-) thymocytes, whereas the inhibitors of Ca(2+) influx and calcineurin, EGTA and FK506, eliminate the hyperresponsiveness [1].
  • Whereas T beta RI levels remained relatively constant, T beta RII expression was strongly induced in TPA-treated skins, prior to the induction of the growth inhibitory response to TGF-beta 1, and its level of expression correlated with growth sensitivity to TGF-beta 1 in vivo and in vitro [28].
  • In contrast, none of the mice repopulated with TGF-beta1(-/-) cells (chimerism > 70%) showed deposition of reticulin fibers at any time during the follow-up [4].
  • Members of the transforming growth factor-beta (TGF-beta) superfamily signal via different heteromeric complexes of two sequentially acting serine/threonine kinase receptors, i.e. type I and type II receptors [30].
  • Moreover, the co-administration of SB203580 and ALK5I to ADR-injected mice resulted in a down-regulation of total and active TGF-beta1 production, reduced myofibroblast accumulation, and decreased expression of collagen type IV and fibronectin [31].
  • Our data demonstrate that insulin-specific regulatory cells protect from diabetes by virtue of their production of TGF-beta1 that acts in an autocrine manner to maintain their regulatory function and acts in a paracrine manner on the target cells [32].
  • The in vitro and in vivo induction of chondrogenesis by Pb likely involves modulation and integration of multiple signaling pathways including TGF-beta, BMP, AP-1, and NFkappaB [33].

Physical interactions of Tgfb1

  • Betaglycan is a membrane-anchored proteoglycan co-receptor that binds transforming growth factor beta (TGF-beta) via its core protein and basic fibroblast growth factor through its glycosaminoglycan chains [34].
  • We have previously shown that both transforming growth factor-beta (TGF-beta) and retinoic acid (RA) regulate the expression of cellular retinoic acid binding proteins (CRABP) I and II and TGF-beta 3 mRNAs in primary cultures of murine embryonic palate mesenchymal (MEPM) cells [35].
  • Analysis of mutant promoters revealed that the one putative HIF-1 and two Smad-binding elements were critical for TGF-beta1-induced VEGF promoter activity [36].
  • Fibronectin is required for integrin alphavbeta6-mediated activation of latent TGF-beta complexes containing LTBP-1 [37].
  • BACKGROUND: In endothelial cells (EC), transforming growth factor-beta (TGF-beta) can bind to and transduce signals through ALK1 and ALK5 [38].

Enzymatic interactions of Tgfb1

  • Neither TGFbeta-dependent nor endogenously phosphorylated Smad2/3 was detectable in comparable amounts in transdifferentiated MFB, indicating loss of TGFbeta sensitivity [39].
  • TGFbeta superfamily members signal through specific cell surface receptors that phosphorylate the cytoplasmic Smad proteins, resulting in their translocation to the nucleus and interaction with promoters of TGFbeta-responsive genes [40].

Co-localisations of Tgfb1


Regulatory relationships of Tgfb1


Other interactions of Tgfb1


Analytical, diagnostic and therapeutic context of Tgfb1


  1. TGF beta 1 inhibits Ca2+-calcineurin-mediated activation in thymocytes. Bommireddy, R., Ormsby, I., Yin, M., Boivin, G.P., Babcock, G.F., Doetschman, T. J. Immunol. (2003) [Pubmed]
  2. TGF beta 1 inhibits NF-kappa B/Rel activity inducing apoptosis of B cells: transcriptional activation of I kappa B alpha. Arsura, M., Wu, M., Sonenshein, G.E. Immunity (1996) [Pubmed]
  3. The cysteine-rich domain protein KCP is a suppressor of transforming growth factor beta/activin signaling in renal epithelia. Lin, J., Patel, S.R., Wang, M., Dressler, G.R. Mol. Cell. Biol. (2006) [Pubmed]
  4. Prominent role of TGF-beta 1 in thrombopoietin-induced myelofibrosis in mice. Chagraoui, H., Komura, E., Tulliez, M., Giraudier, S., Vainchenker, W., Wendling, F. Blood (2002) [Pubmed]
  5. Hematopoietic cytokines inhibit apoptosis induced by transforming growth factor beta 1 and cancer chemotherapy compounds in myeloid leukemic cells. Lotem, J., Sachs, L. Blood (1992) [Pubmed]
  6. Enhanced hepatocyte growth factor signaling by type II transforming growth factor-beta receptor knockout fibroblasts promotes mammary tumorigenesis. Cheng, N., Chytil, A., Shyr, Y., Joly, A., Moses, H.L. Cancer Res. (2007) [Pubmed]
  7. Erythropoietin decreases renal fibrosis in mice with ureteral obstruction: role of inhibiting TGF-beta-induced epithelial-to-mesenchymal transition. Park, S.H., Choi, M.J., Song, I.K., Choi, S.Y., Nam, J.O., Kim, C.D., Lee, B.H., Park, R.W., Park, K.M., Kim, Y.J., Kim, I.S., Kwon, T.H., Kim, Y.L. J. Am. Soc. Nephrol. (2007) [Pubmed]
  8. Dual roles of immunoregulatory cytokine TGF-beta in the pathogenesis of autoimmunity-mediated organ damage. Saxena, V., Lienesch, D.W., Zhou, M., Bommireddy, R., Azhar, M., Doetschman, T., Singh, R.R. J. Immunol. (2008) [Pubmed]
  9. TGFbeta inhibition of yolk-sac-like differentiation of human embryonic stem-cell-derived embryoid bodies illustrates differences between early mouse and human development. Poon, E., Clermont, F., Firpo, M.T., Akhurst, R.J. J. Cell. Sci. (2006) [Pubmed]
  10. Functional role of TGF beta in Alzheimer's disease microvascular injury: lessons from transgenic mice. Masliah, E., Ho, G., Wyss-Coray, T. Neurochem. Int. (2001) [Pubmed]
  11. Autoimmune manifestations in the transforming growth factor-beta 1 knockout mouse. Yaswen, L., Kulkarni, A.B., Fredrickson, T., Mittleman, B., Schiffman, R., Payne, S., Longenecker, G., Mozes, E., Karlsson, S. Blood (1996) [Pubmed]
  12. Microglial activation varies in different models of Creutzfeldt-Jakob disease. Baker, C.A., Lu, Z.Y., Zaitsev, I., Manuelidis, L. J. Virol. (1999) [Pubmed]
  13. Alcohol and hepatitis C virus core protein additively increase lipid peroxidation and synergistically trigger hepatic cytokine expression in a transgenic mouse model. Perlemuter, G., Lettéron, P., Carnot, F., Zavala, F., Pessayre, D., Nalpas, B., Bréchot, C. J. Hepatol. (2003) [Pubmed]
  14. The Orphan Nuclear Receptor RORgammat Directs the Differentiation Program of Proinflammatory IL-17(+) T Helper Cells. Ivanov, I.I., McKenzie, B.S., Zhou, L., Tadokoro, C.E., Lepelley, A., Lafaille, J.J., Cua, D.J., Littman, D.R. Cell (2006) [Pubmed]
  15. Ubiquitin-mediated degradation a mechanism for fine-tuning TGF-beta signaling. Datto, M., Wang, X.F. Cell (2005) [Pubmed]
  16. Causal relationship between the loss of RUNX3 expression and gastric cancer. Li, Q.L., Ito, K., Sakakura, C., Fukamachi, H., Inoue, K., Chi, X.Z., Lee, K.Y., Nomura, S., Lee, C.W., Han, S.B., Kim, H.M., Kim, W.J., Yamamoto, H., Yamashita, N., Yano, T., Ikeda, T., Itohara, S., Inazawa, J., Abe, T., Hagiwara, A., Yamagishi, H., Ooe, A., Kaneda, A., Sugimura, T., Ushijima, T., Bae, S.C., Ito, Y. Cell (2002) [Pubmed]
  17. Regulation of left-right patterning in mice by growth/differentiation factor-1. Rankin, C.T., Bunton, T., Lawler, A.M., Lee, S.J. Nat. Genet. (2000) [Pubmed]
  18. Cultured tubule cells from TGF-beta1 null mice exhibit impaired hypertrophy and fibronectin expression in high glucose. Chen, S., Hoffman, B.B., Lee, J.S., Kasama, Y., Jim, B., Kopp, J.B., Ziyadeh, F.N. Kidney Int. (2004) [Pubmed]
  19. 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]
  20. Effects of dietary omega3 and omega6 lipids and vitamin E on proliferative response, lymphoid cell subsets, production of cytokines by spleen cells, and splenic protein levels for cytokines and oncogenes in MRL/MpJ-lpr/lpr mice. Venkatraman, J.T., Chu, W.C. J. Nutr. Biochem. (1999) [Pubmed]
  21. Beta3 integrin and Src facilitate transforming growth factor-beta mediated induction of epithelial-mesenchymal transition in mammary epithelial cells. Galliher, A.J., Schiemann, W.P. Breast Cancer Res. (2006) [Pubmed]
  22. Conditional overexpression of active transforming growth factor beta1 in vivo accelerates metastases of transgenic mammary tumors. Muraoka-Cook, R.S., Kurokawa, H., Koh, Y., Forbes, J.T., Roebuck, L.R., Barcellos-Hoff, M.H., Moody, S.E., Chodosh, L.A., Arteaga, C.L. Cancer Res. (2004) [Pubmed]
  23. Mapping of a major genetic modifier of embryonic lethality in TGF beta 1 knockout mice. Bonyadi, M., Rusholme, S.A., Cousins, F.M., Su, H.C., Biron, C.A., Farrall, M., Akhurst, R.J. Nat. Genet. (1997) [Pubmed]
  24. Delayed wound healing in immunodeficient TGF-beta 1 knockout mice. Crowe, M.J., Doetschman, T., Greenhalgh, D.G. J. Invest. Dermatol. (2000) [Pubmed]
  25. Strain dependency of TGFbeta1 function during embryogenesis. Kallapur, S., Ormsby, I., Doetschman, T. Mol. Reprod. Dev. (1999) [Pubmed]
  26. Accelerated re-epithelialization in beta3-integrin-deficient- mice is associated with enhanced TGF-beta1 signaling. Reynolds, L.E., Conti, F.J., Lucas, M., Grose, R., Robinson, S., Stone, M., Saunders, G., Dickson, C., Hynes, R.O., Lacy-Hulbert, A., Hodivala-Dilke, K. Nat. Med. (2005) [Pubmed]
  27. TGF-beta 1 regulates lymphocyte homeostasis by preventing activation and subsequent apoptosis of peripheral lymphocytes. Bommireddy, R., Saxena, V., Ormsby, I., Yin, M., Boivin, G.P., Babcock, G.F., Singh, R.R., Doetschman, T. J. Immunol. (2003) [Pubmed]
  28. Concerted action of TGF-beta 1 and its type II receptor in control of epidermal homeostasis in transgenic mice. Cui, W., Fowlis, D.J., Cousins, F.M., Duffie, E., Bryson, S., Balmain, A., Akhurst, R.J. Genes Dev. (1995) [Pubmed]
  29. TGF-beta inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3. Liu, D., Black, B.L., Derynck, R. Genes Dev. (2001) [Pubmed]
  30. Transforming growth factor (TGF-beta)-specific signaling by chimeric TGF-beta type II receptor with intracellular domain of activin type IIB receptor. Persson, U., Souchelnytskyi, S., Franzén, P., Miyazono, K., ten Dijke, P., Heldin, C.H. J. Biol. Chem. (1997) [Pubmed]
  31. Inhibition of p38 Mitogen-Activated Protein Kinase and Transforming Growth Factor-{beta}1/Smad Signaling Pathways Modulates the Development of Fibrosis in Adriamycin-Induced Nephropathy. Li, J., Campanale, N.V., Liang, R.J., Deane, J.A., Bertram, J.F., Ricardo, S.D. Am. J. Pathol. (2006) [Pubmed]
  32. TGF-beta signaling is required for the function of insulin-reactive T regulatory cells. Du, W., Wong, F.S., Li, M.O., Peng, J., Qi, H., Flavell, R.A., Sherwin, R., Wen, L. J. Clin. Invest. (2006) [Pubmed]
  33. Lead induces chondrogenesis and alters transforming growth factor-beta and bone morphogenetic protein signaling in mesenchymal cell populations. Zuscik, M.J., Ma, L., Buckley, T., Puzas, J.E., Drissi, H., Schwarz, E.M., O'Keefe, R.J. Environ. Health Perspect. (2007) [Pubmed]
  34. Betaglycan expression is transcriptionally up-regulated during skeletal muscle differentiation. Cloning of murine betaglycan gene promoter and its modulation by MyoD, retinoic acid, and transforming growth factor-beta. Lopez-Casillas, F., Riquelme, C., Perez-Kato, Y., Ponce-Castaneda, M.V., Osses, N., Esparza-Lopez, J., Gonzalez-Nunez, G., Cabello-Verrugio, C., Mendoza, V., Troncoso, V., Brandan, E. J. Biol. Chem. (2003) [Pubmed]
  35. TGF-beta modulates the expression of retinoic acid-induced RAR-beta in primary cultures of embryonic palate cells. Nugent, P., Potchinsky, M., Lafferty, C., Greene, R.M. Exp. Cell Res. (1995) [Pubmed]
  36. Mechanisms underlying TGF-{beta}1-induced expression of VEGF and Flk-1 in mouse macrophages and their implications for angiogenesis. Jeon, S.H., Chae, B.C., Kim, H.A., Seo, G.Y., Seo, D.W., Chun, G.T., Kim, N.S., Yie, S.W., Byeon, W.H., Eom, S.H., Ha, K.S., Kim, Y.M., Kim, P.H. J. Leukoc. Biol. (2007) [Pubmed]
  37. Fibronectin is required for integrin alphavbeta6-mediated activation of latent TGF-beta complexes containing LTBP-1. Fontana, L., Chen, Y., Prijatelj, P., Sakai, T., Fässler, R., Sakai, L.Y., Rifkin, D.B. FASEB J. (2005) [Pubmed]
  38. Smad7 and protein phosphatase 1alpha are critical determinants in the duration of TGF-beta/ALK1 signaling in endothelial cells. Valdimarsdottir, G., Goumans, M.J., Itoh, F., Itoh, S., Heldin, C.H., ten Dijke, P. BMC Cell Biol. (2006) [Pubmed]
  39. Transforming growth factor beta signal transduction in hepatic stellate cells via Smad2/3 phosphorylation, a pathway that is abrogated during in vitro progression to myofibroblasts. TGFbeta signal transduction during transdifferentiation of hepatic stellate cells. Dooley, S., Delvoux, B., Streckert, M., Bonzel, L., Stopa, M., ten Dijke, P., Gressner, A.M. FEBS Lett. (2001) [Pubmed]
  40. Functional interaction between Smad, CREB binding protein, and p68 RNA helicase. Warner, D.R., Bhattacherjee, V., Yin, X., Singh, S., Mukhopadhyay, P., Pisano, M.M., Greene, R.M. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  41. Transforming growth factor-beta stimulates cyclin D1 expression through activation of beta-catenin signaling in chondrocytes. Li, T.F., Chen, D., Wu, Q., Chen, M., Sheu, T.J., Schwarz, E.M., Drissi, H., Zuscik, M., O'Keefe, R.J. J. Biol. Chem. (2006) [Pubmed]
  42. JNK regulates autocrine expression of TGF-beta1. Ventura, J.J., Kennedy, N.J., Flavell, R.A., Davis, R.J. Mol. Cell (2004) [Pubmed]
  43. Massive hepatic apoptosis associated with TGF-beta1 activation after Fas ligand treatment of IGF binding protein-1-deficient mice. Leu, J.I., Crissey, M.A., Taub, R. J. Clin. Invest. (2003) [Pubmed]
  44. Cell size and invasion in TGF-beta-induced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway. Lamouille, S., Derynck, R. J. Cell Biol. (2007) [Pubmed]
  45. Upregulation of two BH3-only proteins, Bmf and Bim, during TGF beta-induced apoptosis. Ramjaun, A.R., Tomlinson, S., Eddaoudi, A., Downward, J. Oncogene (2007) [Pubmed]
  46. FAK is required for TGFbeta-induced JNK phosphorylation in fibroblasts: implications for acquisition of a matrix-remodeling phenotype. Liu, S., Xu, S.W., Kennedy, L., Pala, D., Chen, Y., Eastwood, M., Carter, D.E., Black, C.M., Abraham, D.J., Leask, A. Mol. Biol. Cell (2007) [Pubmed]
  47. Phosphorylation of the cyclic AMP response element binding protein mediates transforming growth factor beta-induced downregulation of cyclin A in vascular smooth muscle cells. Kamiya, K., Sakakibara, K., Ryer, E.J., Hom, R.P., Leof, E.B., Kent, K.C., Liu, B. Mol. Cell. Biol. (2007) [Pubmed]
  48. TGF-beta signaling is essential for joint morphogenesis. Spagnoli, A., O'Rear, L., Chandler, R.L., Granero-Molto, F., Mortlock, D.P., Gorska, A.E., Weis, J.A., Longobardi, L., Chytil, A., Shimer, K., Moses, H.L. J. Cell Biol. (2007) [Pubmed]
  49. Astrocyte-derived TGF-beta 2 and NGF differentially regulate neural recognition molecule expression by cultured astrocytes. Saad, B., Constam, D.B., Ortmann, R., Moos, M., Fontana, A., Schachner, M. J. Cell Biol. (1991) [Pubmed]
  50. Transforming growth factor beta up-regulates cysteine-rich protein 2 in vascular smooth muscle cells via activating transcription factor 2. Lin, D.W., Chang, I.C., Tseng, A., Wu, M.L., Chen, C.H., Patenaude, C.A., Layne, M.D., Yet, S.F. J. Biol. Chem. (2008) [Pubmed]
  51. Snail is required for TGFbeta-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells. Kokudo, T., Suzuki, Y., Yoshimatsu, Y., Yamazaki, T., Watabe, T., Miyazono, K. J. Cell. Sci. (2008) [Pubmed]
  52. Jun N-terminal kinase 1 regulates epithelial-to-mesenchymal transition induced by TGF-beta1. Alcorn, J.F., Guala, A.S., van der Velden, J., McElhinney, B., Irvin, C.G., Davis, R.J., Janssen-Heininger, Y.M. J. Cell. Sci. (2008) [Pubmed]
  53. Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice. Larsson, J., Goumans, M.J., Sjöstrand, L.J., van Rooijen, M.A., Ward, D., Levéen, P., Xu, X., ten Dijke, P., Mummery, C.L., Karlsson, S. EMBO J. (2001) [Pubmed]
  54. Altered T-cell receptor + CD28-mediated signaling and blocked cell cycle progression in interleukin 10 and transforming growth factor-beta-treated alloreactive T cells that do not induce graft-versus-host disease. Boussiotis, V.A., Chen, Z.M., Zeller, J.C., Murphy, W.J., Berezovskaya, A., Narula, S., Roncarolo, M.G., Blazar, B.R. Blood (2001) [Pubmed]
  55. Maintenance of murine long-term repopulating stem cells in ex vivo culture is affected by modulation of transforming growth factor-beta but not macrophage inflammatory protein-1 alpha activities. Soma, T., Yu, J.M., Dunbar, C.E. Blood (1996) [Pubmed]
  56. Localization of cells synthesizing transforming growth factor-alpha mRNA in the mouse brain. Wilcox, J.N., Derynck, R. J. Neurosci. (1988) [Pubmed]
  57. TGFbeta2 mediates the effects of hedgehog on hypertrophic differentiation and PTHrP expression. Alvarez, J., Sohn, P., Zeng, X., Doetschman, T., Robbins, D.J., Serra, R. Development (2002) [Pubmed]
WikiGenes - Universities