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Gene Review

Tgfb1  -  transforming growth factor, beta 1

Rattus norvegicus

Synonyms: TGF-beta-1, Transforming growth factor beta-1
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Disease relevance of Tgfb1

  • Together, these findings identify the TGF-beta isoforms as major factors mediating adventitial fibrosis and negative remodeling after vascular injury, a major cause of restenosis after angioplasty [1].
  • Nuclear localization of Smad2/Smad3 indicated that the TGF-beta signaling pathway was activated in regressing carcinomas [2].
  • We examined a rat model of mesangial proliferative glomerulonephritis, where TGF-beta has been demonstrated to mediate renal fibrosis [3].
  • Our study suggests that TGF-beta 1 gene transfer suppresses hepatic granuloma formation by blocking the recruitment of inflammatory cells to the liver, and thus may provide a new approach to the control of hepatic granulomatous and fibrotic diseases [4].
  • These results demonstrate that TSP1 is the major endogenous activator of TGF-beta in experimental inflammatory kidney disease [3].

Psychiatry related information on Tgfb1


High impact information on Tgfb1

  • Here we describe a new gene, Bog (for B5T over-expressed gene), which was identified and shown to be overexpressed in several transformed rat liver epithelial (RLE) cell lines resistant to the growth-inhibitory effect of TGF-beta1, as well as in primary human liver tumours [10].
  • Introduction of the cDNA into COS cells and L6 myoblasts induces expression of a heterogenously glycosylated 280-330 kd protein characteristic of the type III receptor that binds TGF-beta 1 specifically [11].
  • The rat TGF-beta type III receptor cDNA has been cloned by overexpression in COS cells [11].
  • Transforming growth factor-beta (TGF-beta) increases the steady-state RNA levels of several fibroblast extracellular matrix proteins [12].
  • Deletion analysis indicates that a segment of this promoter between -350 and -300, overlapping a nuclear factor 1 (NF1) binding site, is needed for TGF-beta stimulation [12].

Chemical compound and disease context of Tgfb1


Biological context of Tgfb1

  • Our results suggest that the signal transduction pathway for TGF-beta, leading to apoptosis, is activated in the normal prostate after castration and in the tumor model after castration, without or with estrogen treatment [18].
  • A detailed study on bcl-2 superfamily gene expression shows that TGF-beta produces a decrease in the messenger RNA (mRNA) and protein levels of bcl-x(L), an antiapoptotic member of this family, capable of preventing cytochrome c release [19].
  • PI 3-kinase inhibitors completely block the protective effect of EGF on TGF-beta-induced bcl-x(L )down-regulation [19].
  • These results are discussed in the context of the knowledge of TGF-beta receptor complexity and signal transduction, and with reference to the potential role for loss of TGF-beta-mediated negative growth regulation in malignant transformation [20].
  • We have reported that over expression of the H-ras oncogene causes resistance to growth inhibition by transforming growth factor beta 1 (TGF-beta 1) and a time-dependant switch of type II to type I TGF-beta receptor expression in the rat intestinal epithelial cell line IEC-18 (J. Filmus, J. Zhao, and R. N. Buick, Oncogene, 7: 521-526, 1992) [20].

Anatomical context of Tgfb1


Associations of Tgfb1 with chemical compounds


Physical interactions of Tgfb1

  • At the cell surface, TGF-beta binds to serine-threonine kinase transmembrane receptors (type II and type I) to initiate Smad-dependent intracellular signaling cascades [30].
  • Overexpression of Ets-1 in cultured mesangial cells prevented transforming growth factor (TGF)-beta-induced inhibition of DNA-binding activity and TGF-beta-induced type I collagen production [31].
  • Although TSP1 has been shown to bind active TGF beta 1, this cytokine could not account for the inhibitory effects of the stalk region of TSP1 on cultured endothelial cells [32].
  • Northern blotting demonstrated the difference in the mRNA expression patterns of TGF-beta 1 and latent TGF-beta 1 binding protein (LTBP) in the cortex [33].
  • The effect of TGF-beta was exerted by stabilizing fibronectin mRNA without affecting the promoter activity and required de novo protein synthesis [34].

Enzymatic interactions of Tgfb1

  • Our results demonstrate that Fra-2 is hyperphosphorylated upon TGF-beta 1 treatment of ROS 17/2.8 cells [35].

Co-localisations of Tgfb1


Regulatory relationships of Tgfb1

  • An anti-TGF-beta 1 neutralizing Ab abolished the inhibitory effect exerted by the mesangial cell medium, and externally added TGF-beta 1 suppressed the MCP-1 expression by macrophages at both mRNA and protein levels [38].
  • Overexpression of Smad7 induced by doxycycline results in marked inhibition of TGF-beta-induced Smad2 activation (90% downward arrow) with the prevention of collagen synthesis and myofibroblast transformation [39].
  • Using a normal rat kidney tubular epithelial cell line (NRK52E), it was determined that TGF-beta1 induces Smad2 phosphorylation and nuclear localization in both a dose- and time-dependent manner [39].
  • The increase in CTGF and collagen I induced by LDL was significantly inhibited by neutralizing anti-TGF-beta antibodies [40].
  • Moreover, CT stimulated TGF-beta 1 mRNA expression, as well as TGF-beta 1 synthesis, in a dose-dependent fashion [41].
  • TGF-beta/Smad3-induced MCP-1 was completely blocked by both Ro-32-0432 and rotterlin, suggesting protein kinase C-delta (PKCdelta) may play a role in TGF-beta/Smad3-induced MCP-1 expression [42].

Other interactions of Tgfb1

  • The inhibitory effects of glucagon were observed when the hormone was added either 10 minutes or 60 minutes before EGF addition, whereas no effects of TGF-beta were observed after 10-minute or 60-minute incubation [43].
  • Id1 is a critical mediator in TGF-beta-induced transdifferentiation of rat hepatic stellate cells [44].
  • In both groups, cytokine mRNA levels all returned to baseline levels at 24 hours, while IL-1 beta, TNF-alpha, and TGF-beta 1 mRNA levels again rose significantly at 7 days only in animals with permanent LAD occlusion [45].
  • During early reperfusion, mRNA levels for IL-6 and TGF-beta 1 were significantly reduced compared with permanent LAD occlusion [45].
  • Identification of an inhibitor targeting macrophage production of monocyte chemoattractant protein-1 as TGF-beta 1 [38].

Analytical, diagnostic and therapeutic context of Tgfb1

  • The activity of TGF-beta in the extracts from transplanted as well as normal hearts was measured using a bioassay, and Northern blot analysis was performed on RNA extracts [26].
  • We show that IGF-I does not down-regulate TGF-beta receptor levels, as determined by both receptor cross-linking and Western blot analyses [46].
  • Immunoblot analysis and a specific bioassay detected the active form of TGF-beta 1 exclusively in the mesangial cell conditioned media [47].
  • The induction of TGF-beta may counteract the rejection process and could be useful for new therapeutic approaches in the prevention of allograft rejection [26].
  • During the acute rejection process up to 6 days after transplantation, TGF-beta immunoreactivity increased only slightly, whereas the TGF-beta mRNA was severalfold increased [26].


  1. Soluble transforming growth factor-beta type II receptor inhibits negative remodeling, fibroblast transdifferentiation, and intimal lesion formation but not endothelial growth. Smith, J.D., Bryant, S.R., Couper, L.L., Vary, C.P., Gotwals, P.J., Koteliansky, V.E., Lindner, V. Circ. Res. (1999) [Pubmed]
  2. Activation of the transforming growth factor beta signaling pathway and induction of cytostasis and apoptosis in mammary carcinomas treated with the anticancer agent perillyl alcohol. Ariazi, E.A., Satomi, Y., Ellis, M.J., Haag, J.D., Shi, W., Sattler, C.A., Gould, M.N. Cancer Res. (1999) [Pubmed]
  3. Antisense oligonucleotides against thrombospondin-1 inhibit activation of tgf-beta in fibrotic renal disease in the rat in vivo. Daniel, C., Takabatake, Y., Mizui, M., Isaka, Y., Kawashi, H., Rupprecht, H., Imai, E., Hugo, C. Am. J. Pathol. (2003) [Pubmed]
  4. Inhibition of bacterial cell wall-induced leukocyte recruitment and hepatic granuloma formation by TGF-beta gene transfer. Song, X., Zeng, L., Pilo, C.M., Zagorski, J., Wahl, S.M. J. Immunol. (1999) [Pubmed]
  5. Transfer of the active form of transforming growth factor-beta 1 gene to newborn rat lung induces changes consistent with bronchopulmonary dysplasia. Gauldie, J., Galt, T., Bonniaud, P., Robbins, C., Kelly, M., Warburton, D. Am. J. Pathol. (2003) [Pubmed]
  6. Clusterin expression by astrocytes is influenced by transforming growth factor beta 1 and heterotypic cell interactions. Morgan, T.E., Laping, N.J., Rozovsky, I., Oda, T., Hogan, T.H., Finch, C.E., Pasinetti, G.M. J. Neuroimmunol. (1995) [Pubmed]
  7. Transforming growth factor-beta activated during exercise in brain depresses spontaneous motor activity of animals. Relevance To central fatigue. Inoue, K., Yamazaki, H., Manabe, Y., Fukuda, C., Hanai, K., Fushiki, T. Brain Res. (1999) [Pubmed]
  8. Expression of transforming growth factor-beta1 in penile tissue from rats with bilateral cavernosal nerve ablation. Hu, W.L., Hu, L.Q., Li, S.W., Zheng, X.M., Tian, B.C. BJU international. (2004) [Pubmed]
  9. Rat mandibular distraction osteogenesis: II. Molecular analysis of transforming growth factor beta-1 and osteocalcin gene expression. Mehrara, B.J., Rowe, N.M., Steinbrech, D.S., Dudziak, M.E., Saadeh, P.B., McCarthy, J.G., Gittes, G.K., Longaker, M.T. Plast. Reconstr. Surg. (1999) [Pubmed]
  10. A retinoblastoma-binding protein that affects cell-cycle control and confers transforming ability. Woitach, J.T., Zhang, M., Niu, C.H., Thorgeirsson, S.S. Nat. Genet. (1998) [Pubmed]
  11. Expression cloning and characterization of the TGF-beta type III receptor. Wang, X.F., Lin, H.Y., Ng-Eaton, E., Downward, J., Lodish, H.F., Weinberg, R.A. Cell (1991) [Pubmed]
  12. A nuclear factor 1 binding site mediates the transcriptional activation of a type I collagen promoter by transforming growth factor-beta. Rossi, P., Karsenty, G., Roberts, A.B., Roche, N.S., Sporn, M.B., de Crombrugghe, B. Cell (1988) [Pubmed]
  13. Combining TGF-beta inhibition and angiotensin II blockade results in enhanced antifibrotic effect. Yu, L., Border, W.A., Anderson, I., McCourt, M., Huang, Y., Noble, N.A. Kidney Int. (2004) [Pubmed]
  14. Gene therapy by transforming growth factor-beta receptor-IgG Fc chimera suppressed extracellular matrix accumulation in experimental glomerulonephritis. Isaka, Y., Akagi, Y., Ando, Y., Tsujie, M., Sudo, T., Ohno, N., Border, W.A., Noble, N.A., Kaneda, Y., Hori, M., Imai, E. Kidney Int. (1999) [Pubmed]
  15. Basic fibroblast growth factor induces TGF-beta release in an isoform and glioma-specific manner. Dhandapani, K.M., Wade, M.F., Mahesh, V.B., Brann, D.W. Neuroreport (2002) [Pubmed]
  16. Norepinephrine enhances fibrosis mediated by TGF-beta in cardiac fibroblasts. Akiyama-Uchida, Y., Ashizawa, N., Ohtsuru, A., Seto, S., Tsukazaki, T., Kikuchi, H., Yamashita, S., Yano, K. Hypertension (2002) [Pubmed]
  17. JinSanE Decoction, A Chinese Herbal Medicine, Inhibits Expression of TGF-beta1/Smads in Experimental Hepatic Fibrosis in Rats. Song, S.L., Gong, Z.J., Huang, Y.Q., Zhang, Q.R., Huang, T.X. Am. J. Chin. Med. (2006) [Pubmed]
  18. Increased smad expression and activation are associated with apoptosis in normal and malignant prostate after castration. Brodin, G., ten Dijke, P., Funa, K., Heldin, C.H., Landström, M. Cancer Res. (1999) [Pubmed]
  19. Epidermal growth factor impairs the cytochrome C/caspase-3 apoptotic pathway induced by transforming growth factor beta in rat fetal hepatocytes via a phosphoinositide 3-kinase-dependent pathway. Fabregat, I., Herrera, B., Fernández, M., Alvarez, A.M., Sánchez, A., Roncero, C., Ventura, J.J., Valverde, A.M., Benito, M. Hepatology (2000) [Pubmed]
  20. Regulation of transforming growth factor beta receptors in H-ras oncogene-transformed rat intestinal epithelial cells. Zhao, J., Buick, R.N. Cancer Res. (1995) [Pubmed]
  21. Radiation-induced alterations in rat mesangial cell Tgfb1 and Tgfb3 gene expression are not associated with altered secretion of active Tgfb isoforms. O'Malley, Y., Zhao, W., Barcellos-Hoff, M.H., Robbins, M.E. Radiat. Res. (1999) [Pubmed]
  22. Involvement of wound-associated factors in rat brain astrocyte migratory response to axonal injury: in vitro simulation. Faber-Elman, A., Solomon, A., Abraham, J.A., Marikovsky, M., Schwartz, M. J. Clin. Invest. (1996) [Pubmed]
  23. TGF-beta promotes proliferation of cultured SMC via both PDGF-AA-dependent and PDGF-AA-independent mechanisms. Stouffer, G.A., Owens, G.K. J. Clin. Invest. (1994) [Pubmed]
  24. Cytokine modulation of intestinal epithelial cell restitution: central role of transforming growth factor beta. Dignass, A.U., Podolsky, D.K. Gastroenterology (1993) [Pubmed]
  25. Glucose up-regulates thrombospondin 1 gene transcription and transforming growth factor-beta activity through antagonism of cGMP-dependent protein kinase repression via upstream stimulatory factor 2. Wang, S., Skorczewski, J., Feng, X., Mei, L., Murphy-Ullrich, J.E. J. Biol. Chem. (2004) [Pubmed]
  26. Induction of transforming growth factor-beta during cardiac allograft rejection. Waltenberger, J., Wanders, A., Fellström, B., Miyazono, K., Heldin, C.H., Funa, K. J. Immunol. (1993) [Pubmed]
  27. Ursodeoxycholic acid modulates E2F-1 and p53 expression through a caspase-independent mechanism in transforming growth factor beta1-induced apoptosis of rat hepatocytes. Sola, S., Ma, X., Castro, R.E., Kren, B.T., Steer, C.J., Rodrigues, C.M. J. Biol. Chem. (2003) [Pubmed]
  28. The functional interaction between the paired domain transcription factor Pax8 and Smad3 is involved in transforming growth factor-beta repression of the sodium/iodide symporter gene. Costamagna, E., García, B., Santisteban, P. J. Biol. Chem. (2004) [Pubmed]
  29. The synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid-imidazolide alters transforming growth factor beta-dependent signaling and cell migration by affecting the cytoskeleton and the polarity complex. To, C., Kulkarni, S., Pawson, T., Honda, T., Gribble, G.W., Sporn, M.B., Wrana, J.L., Di Guglielmo, G.M. J. Biol. Chem. (2008) [Pubmed]
  30. Transforming growth factor beta (TGF-beta) signaling is regulated by electrical activity in skeletal muscle cells. TGF-beta type I receptor is transcriptionally regulated by myotube excitability. Ugarte, G., Brandan, E. J. Biol. Chem. (2006) [Pubmed]
  31. Transcription factor Ets-1 is essential for mesangial matrix remodeling. Mizui, M., Isaka, Y., Takabatake, Y., Sato, Y., Kawachi, H., Shimizu, F., Takahara, S., Ito, T., Imai, E. Kidney Int. (2006) [Pubmed]
  32. Peptides derived from two separate domains of the matrix protein thrombospondin-1 have anti-angiogenic activity. Tolsma, S.S., Volpert, O.V., Good, D.J., Frazier, W.A., Polverini, P.J., Bouck, N. J. Cell Biol. (1993) [Pubmed]
  33. TGF-beta 1 in glomerulosclerosis and interstitial fibrosis of adriamycin nephropathy. Tamaki, K., Okuda, S., Ando, T., Iwamoto, T., Nakayama, M., Fujishima, M. Kidney Int. (1994) [Pubmed]
  34. Angiotensin II-induced transactivation of epidermal growth factor receptor regulates fibronectin and transforming growth factor-beta synthesis via transcriptional and posttranscriptional mechanisms. Moriguchi, Y., Matsubara, H., Mori, Y., Murasawa, S., Masaki, H., Maruyama, K., Tsutsumi, Y., Shibasaki, Y., Tanaka, Y., Nakajima, T., Oda, K., Iwasaka, T. Circ. Res. (1999) [Pubmed]
  35. Transforming growth factor-beta 1 responsiveness of the rat osteocalcin gene is mediated by an activator protein-1 binding site. Banerjee, C., Stein, J.L., Van Wijnen, A.J., Frenkel, B., Lian, J.B., Stein, G.S. Endocrinology (1996) [Pubmed]
  36. Expression of hepatocyte growth factor mRNA in rat liver cirrhosis induced by N-nitrosodimethylamine as evidenced by in situ RT-PCR. Hata, J., Ikeda, E., Uno, H., Asano, S. J. Histochem. Cytochem. (2002) [Pubmed]
  37. Site-specific responses to monocrotaline-induced vascular injury: evidence for two distinct mechanisms of remodeling. Tanaka, Y., Bernstein, M.L., Mecham, R.P., Patterson, G.A., Cooper, J.D., Botney, M.D. Am. J. Respir. Cell Mol. Biol. (1996) [Pubmed]
  38. Identification of an inhibitor targeting macrophage production of monocyte chemoattractant protein-1 as TGF-beta 1. Kitamura, M. J. Immunol. (1997) [Pubmed]
  39. Smad7 inhibits fibrotic effect of TGF-Beta on renal tubular epithelial cells by blocking Smad2 activation. Li, J.H., Zhu, H.J., Huang, X.R., Lai, K.N., Johnson, R.J., Lan, H.Y. J. Am. Soc. Nephrol. (2002) [Pubmed]
  40. Evidence for low-density lipoprotein-induced expression of connective tissue growth factor in mesangial cells. Sohn, M., Tan, Y., Klein, R.L., Jaffa, A.A. Kidney Int. (2005) [Pubmed]
  41. Antiproliferative action of calcitonin on lactotrophs of the rat anterior pituitary gland: evidence for the involvement of transforming growth factor beta 1 in calcitonin action. Wang, Y.Q., Yuan, R., Sun, Y.P., Lee, T.J., Shah, G.V. Endocrinology (2003) [Pubmed]
  42. Transforming growth factor-beta promotes recruitment of bone marrow cells and bone marrow-derived mesenchymal stem cells through stimulation of MCP-1 production in vascular smooth muscle cells. Zhang, F., Tsai, S., Kato, K., Yamanouchi, D., Wang, C., Rafii, S., Liu, B., Kent, K.C. J. Biol. Chem. (2009) [Pubmed]
  43. Inhibition of rat hepatocyte proliferation by transforming growth factor beta and glucagon is associated with inhibition of ERK2 and p70 S6 kinase. Dixon, M., Agius, L., Yeaman, S.J., Day, C.P. Hepatology (1999) [Pubmed]
  44. Id1 is a critical mediator in TGF-beta-induced transdifferentiation of rat hepatic stellate cells. Wiercinska, E., Wickert, L., Denecke, B., Said, H.M., Hamzavi, J., Gressner, A.M., Thorikay, M., ten Dijke, P., Mertens, P.R., Breitkopf, K., Dooley, S. Hepatology (2006) [Pubmed]
  45. Cytokine mRNA expression in postischemic/reperfused myocardium. Herskowitz, A., Choi, S., Ansari, A.A., Wesselingh, S. Am. J. Pathol. (1995) [Pubmed]
  46. Insulin-like growth factor-I inhibits transcriptional responses of transforming growth factor-beta by phosphatidylinositol 3-kinase/Akt-dependent suppression of the activation of Smad3 but not Smad2. Song, K., Cornelius, S.C., Reiss, M., Danielpour, D. J. Biol. Chem. (2003) [Pubmed]
  47. Transforming growth factor-beta 1 is the predominant paracrine inhibitor of macrophage cytokine synthesis produced by glomerular mesangial cells . Kitamura, M., Sütö, T., Yokoo, T., Shimizu, F., Fine, L.G. J. Immunol. (1996) [Pubmed]
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