TGF beta 1

{{see also|TGF beta signaling pathway}}

TGF-β is a multifunctional set of peptides that controls proliferation, differentiation, and other functions in many cell types. TGF-β acts synergistically with transforming growth factor-alpha (TGF-α) in inducing transformation. It also acts as a negative autocrine growth factor. Dysregulation of TGF-β activation and signaling may result in apoptosis. Many cells synthesize TGF-β and almost all of them have specific receptors for this peptide. TGF-β1, TGF-β2, and TGF-β3 all function through the same receptor signaling systems.{{cite web | title = Entrez Gene: TGFB1 transforming growth factor, beta 1 | url = https://www.ncbi.nlm.nih.gov/gene/7040 }}

TGF-β1 was first identified in human platelets as a protein with a molecular mass of 25 kilodaltons with a potential role in wound healing.{{cite journal | vauthors = Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB | title = Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization | journal = Journal of Biological Chemistry | volume = 258 | issue = 11 | pages = 7155–7160 | date = Jun 1983 | pmid = 6602130 | doi = 10.1016/S0021-9258(18)32345-7 | doi-access = free }}{{cite journal | vauthors = Custo S, Baron B, Felice A, Seria E | title = A comparative profile of total protein and six angiogenically-active growth factors in three platelet products | journal = GMS Interdisciplinary Plastic and Reconstructive Surgery DGPW | volume = 11 | issue = Doc06 | pages = Doc06 | date = 5 July 2022 | pmid = 35909816 | pmc = 9284722 | doi = 10.3205/iprs000167 | url = https://www.egms.de/static/en/journals/iprs/2022-11/iprs000167.shtml#block5 }} It was later characterized as a large protein precursor (containing 390 amino acids) that was proteolytically processed to produce a mature peptide of 112 amino acids.{{cite journal | vauthors = Derynck R, Jarrett JA, Chen EY, Eaton DH, Bell JR, Assoian RK, Roberts AB, Sporn MB, Goeddel DV | title = Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells | journal = Nature | volume = 316 | issue = 6030 | pages = 701–705 | year = 1985 | pmid = 3861940 | doi = 10.1038/316701a0 | bibcode = 1985Natur.316..701D | s2cid = 4245501 | url = https://zenodo.org/record/1233037 }}

TGF-β1 plays an important role in controlling the immune system, and shows different activities on different types of cell, or cells at different developmental stages. Most immune cells (or leukocytes) secrete TGF-β1.{{cite journal | vauthors = Letterio JJ, Roberts AB | title = Regulation of immune responses by TGF-beta | journal = Annual Review of Immunology | volume = 16 | pages = 137–161 | year = 1998 | pmid = 9597127 | doi = 10.1146/annurev.immunol.16.1.137 | url = https://zenodo.org/record/1234983 }}

Some T cells (e.g. regulatory T cells) release TGF-β1 to inhibit the actions of other T cells. Specifically, TGF-β1 prevents the interleukin(IL)-1- & interleukin-2-dependent proliferation in activated T cells,{{cite journal | vauthors = Wahl SM, Hunt DA, Wong HL, Dougherty S, McCartney-Francis N, Wahl LM, Ellingsworth L, Schmidt JA, Hall G, Roberts AB | title = Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation | journal = Journal of Immunology | location = Baltimore, Md. | volume = 140 | issue = 9 | pages = 3026–3032 | date = May 1988 | pmid = 3129508 | doi = 10.4049/jimmunol.140.9.3026 | s2cid = 35425214 | doi-access = free }}{{cite journal | vauthors = Tiemessen MM, Kunzmann S, Schmidt-Weber CB, Garssen J, Bruijnzeel-Koomen CA, Knol EF, van Hoffen E | title = Transforming growth factor-beta inhibits human antigen-specific CD4+ T cell proliferation without modulating the cytokine response | journal = International Immunology | volume = 15 | issue = 12 | pages = 1495–1504 | date = Dec 2003 | pmid = 14645158 | doi = 10.1093/intimm/dxg147 | doi-access = free }} as well as the activation of quiescent helper T cells and cytotoxic T cells.{{cite journal | vauthors = Gilbert KM, Thoman M, Bauche K, Pham T, Weigle WO | title = Transforming growth factor-beta 1 induces antigen-specific unresponsiveness in naive T cells | journal = Immunological Investigations | volume = 26 | issue = 4 | pages = 459–472 | date = Jun 1997 | pmid = 9246566 | doi = 10.3109/08820139709022702 }}{{cite journal | vauthors = Wahl SM, Wen J, Moutsopoulos N | title = TGF-beta: a mobile purveyor of immune privilege | journal = Immunological Reviews | volume = 213 | pages = 213–227 | date = Oct 2006 | pmid = 16972906 | doi = 10.1111/j.1600-065X.2006.00437.x | s2cid = 84309271 | url = https://zenodo.org/record/1230716 }} Similarly, TGF-β1 can inhibit the secretion and activity of many other cytokines including interferon-γ, tumor necrosis factor-alpha (TNF-α), and various interleukins. It can also decrease the expression levels of cytokine receptors, such as the IL-2 receptor to down-regulate the activity of immune cells. However, TGF-β1 can also increase the expression of certain cytokines in T cells and promote their proliferation,{{cite journal | vauthors = Zhu H, Wang Z, Yu J, Yang X, He F, Liu Z, Che F, Chen X, Ren H, Hong M, Wang J | title = Role and mechanisms of cytokines in the secondary brain injury after intracerebral hemorrhage | journal = Progress in Neurobiology | volume = 178 | pages = 101610 | date = March 2019 | pmid = 30923023 | doi = 10.1016/j.pneurobio.2019.03.003 | s2cid = 85495400 }} particularly if the cells are immature.

TGF-β1 has similar effects on B cells that also vary according to the differentiation state of the cell. It inhibits proliferation, stimulates apoptosis of B cells,{{cite journal | vauthors = Lebman DA, Edmiston JS | title = The role of TGF-beta in growth, differentiation, and maturation of B lymphocytes | journal = Microbes and Infection | volume = 1 | issue = 15 | pages = 1297–1304 | date = Dec 1999 | pmid = 10611758 | doi = 10.1016/S1286-4579(99)00254-3 | doi-access = free }} and controls the expression of antibody, transferrin and MHC class II proteins on immature and mature B cells.

The effects of TGF-β1 on macrophages and monocytes are predominantly suppressive; this cytokine can inhibit the proliferation of these cells and prevent their production of reactive oxygen (e.g. superoxide (O₂⁻)) and nitrogen (e.g. nitric oxide (NO)) intermediates. However, as with other cell types, TGF-β1 can also have the opposite effect on cells of myeloid origin. For example, TGF-β1 acts as a chemoattractant, directing an immune response to certain pathogens. Likewise, macrophages and monocytes respond to low levels of TGF-β1 in a chemotactic manner. Furthermore, the expression of monocytic cytokines (such as interleukin(IL)-1α, IL-1β, and TNF-α), and macrophage's phagocytic can be increased by the action of TGF-β1.

TGF-β1 reduces the efficacy of the MHC II in astrocytes and dendritic cells, which in turn decreases the activation of appropriate helper T cell populations.{{cite journal | vauthors = Rodríguez LS, Narváez CF, Rojas OL, Franco MA, Ángel J | title = Human myeloid dendritic cells treated with supernatants of rotavirus infected Caco-2 cells induce a poor Th1 response | journal = Cellular Immunology | volume = 272 | issue = 2 | pages = 154–161 | date = 2012-01-01 | pmid = 22082567 | doi = 10.1016/j.cellimm.2011.10.017 | url = https://repository.urosario.edu.co/handle/10336/23645 }}{{cite journal | vauthors = Dong Y, Tang L, Letterio JJ, Benveniste EN | title = The Smad3 protein is involved in TGF-beta inhibition of class II transactivator and class II MHC expression | journal = Journal of Immunology | location = Baltimore, Md. | volume = 167 | issue = 1 | pages = 311–319 | date = July 2001 | pmid = 11418665 | doi = 10.4049/jimmunol.167.1.311 | doi-access = free }}

TGF beta 1 has been shown to interact with:

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• Decorin,{{cite journal | vauthors = Hildebrand A, Romarís M, Rasmussen LM, Heinegård D, Twardzik DR, Border WA, Ruoslahti E | title = Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta | journal = The Biochemical Journal | volume = 302 | issue = Pt 2 | pages = 527–534 | date = September 1994 | pmid = 8093006 | pmc = 1137259 | doi = 10.1042/bj3020527 }}{{cite journal | vauthors = Schönherr E, Broszat M, Brandan E, Bruckner P, Kresse H | title = Decorin core protein fragment Leu155-Val260 interacts with TGF-beta but does not compete for decorin binding to type I collagen | journal = Archives of Biochemistry and Biophysics | volume = 355 | issue = 2 | pages = 241–248 | date = July 1998 | pmid = 9675033 | doi = 10.1006/abbi.1998.0720 }}{{cite journal | vauthors = Takeuchi Y, Kodama Y, Matsumoto T | title = Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity | journal = Journal of Biological Chemistry | volume = 269 | issue = 51 | pages = 32634–32638 | date = Dec 1994 | pmid = 7798269 | doi = 10.1016/S0021-9258(18)31681-8 | doi-access = free }}
• EIF3I{{cite journal | vauthors = Choy L, Derynck R | title = The type II transforming growth factor (TGF)-beta receptor-interacting protein TRIP-1 acts as a modulator of the TGF-beta response | journal = Journal of Biological Chemistry | volume = 273 | issue = 47 | pages = 31455–31462 | date = November 1998 | pmid = 9813058 | doi = 10.1074/jbc.273.47.31455 | doi-access = free }}
• LTBP1,{{cite journal | vauthors = Saharinen J, Keski-Oja J | title = Specific sequence motif of 8-Cys repeats of TGF-beta binding proteins, LTBPs, creates a hydrophobic interaction surface for binding of small latent TGF-beta | journal = Molecular Biology of the Cell | volume = 11 | issue = 8 | pages = 2691–2704 | date = August 2000 | pmid = 10930463 | pmc = 14949 | doi = 10.1091/mbc.11.8.2691 }}
• TGF beta receptor 1,{{cite journal | vauthors = Ebner R, Chen RH, Lawler S, Zioncheck T, Derynck R | title = Determination of type I receptor specificity by the type II receptors for TGF-beta or activin | journal = Science | location = New York, N.Y. | volume = 262 | issue = 5135 | pages = 900–902 | date = November 1993 | pmid = 8235612 | doi = 10.1126/science.8235612 | bibcode = 1993Sci...262..900E }}{{cite journal | vauthors = Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E | title = Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 6 | pages = 2626–2631 | date = March 2000 | pmid = 10716993 | pmc = 15979 | doi = 10.1073/pnas.97.6.2626 | bibcode = 2000PNAS...97.2626O | doi-access = free }} and
• YWHAE.{{cite journal | vauthors = McGonigle S, Beall MJ, Feeney EL, Pearce EJ | title = Conserved role for 14-3-3epsilon downstream of type I TGFbeta receptors | journal = FEBS Letters | volume = 490 | issue = 1–2 | pages = 65–69 | date = February 2001 | pmid = 11172812 | doi = 10.1016/s0014-5793(01)02133-0 | s2cid = 84710903 }}

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• {{cite journal | vauthors = Border WA, Noble NA | title = Transforming growth factor beta in tissue fibrosis | journal = The New England Journal of Medicine | volume = 331 | issue = 19 | pages = 1286–1292 | date = Nov 1994 | pmid = 7935686 | doi = 10.1056/NEJM199411103311907 }}
• {{cite journal | vauthors = Munger JS, Harpel JG, Gleizes PE, Mazzieri R, Nunes I, Rifkin DB | title = Latent transforming growth factor-beta: structural features and mechanisms of activation | journal = Kidney International | volume = 51 | issue = 5 | pages = 1376–1382 | date = May 1997 | pmid = 9150447 | doi = 10.1038/ki.1997.188 | doi-access = free }}
• {{cite journal | vauthors = Iozzo RV | title = The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins | journal = Journal of Biological Chemistry | volume = 274 | issue = 27 | pages = 18843–18846 | date = Jul 1999 | pmid = 10383378 | doi = 10.1074/jbc.274.27.18843 | doi-access = free }}
• {{cite journal | vauthors = Reinhold D, Wrenger S, Kähne T, Ansorge S | title = HIV-1 Tat: immunosuppression via TGF-beta1 induction | journal = Immunology Today | volume = 20 | issue = 8 | pages = 384–385 | date = Aug 1999 | pmid = 10431160 | doi = 10.1016/S0167-5699(99)01497-8 }}
• {{cite journal | vauthors = Yamada Y | title = Association of polymorphisms of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis | journal = Pharmacogenetics | volume = 11 | issue = 9 | pages = 765–771 | date = Dec 2001 | pmid = 11740340 | doi = 10.1097/00008571-200112000-00004 }}
• {{cite book | vauthors = Chen W, Wahl SM | chapter = TGF-β: Receptors, Signaling Pathways and Autoimmunity | title = TGF-beta: receptors, signaling pathways and autoimmunity | volume = 5 | pages = 62–91 | year = 2002 | pmid = 11826761 | doi = 10.1159/000060548 | isbn = 978-3-8055-7308-5 | series = Current Directions in Autoimmunity }}
• {{cite journal | vauthors = Marone M, Bonanno G, Rutella S, Leone G, Scambia G, Pierelli L | title = Survival and cell cycle control in early hematopoiesis: role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21 | journal = Leukemia & Lymphoma | volume = 43 | issue = 1 | pages = 51–57 | date = Jan 2002 | pmid = 11908736 | doi = 10.1080/10428190210195 | s2cid = 28490341 }}
• {{cite journal | vauthors = Schnaper HW, Hayashida T, Hubchak SC, Poncelet AC | title = TGF-beta signal transduction and mesangial cell fibrogenesis | journal = American Journal of Physiology. Renal Physiology | volume = 284 | issue = 2 | pages = F243–F252 | date = Feb 2003 | pmid = 12529270 | doi = 10.1152/ajprenal.00300.2002 | s2cid = 17046094 }}
• {{cite journal | vauthors = Kalluri R, Neilson EG | title = Epithelial-mesenchymal transition and its implications for fibrosis | journal = The Journal of Clinical Investigation | volume = 112 | issue = 12 | pages = 1776–1784 | date = Dec 2003 | pmid = 14679171 | pmc = 297008 | doi = 10.1172/JCI20530 }}
• {{cite journal | vauthors = Grainger DJ | title = Transforming growth factor beta and atherosclerosis: so far, so good for the protective cytokine hypothesis | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 24 | issue = 3 | pages = 399–404 | date = Mar 2004 | pmid = 14699019 | doi = 10.1161/01.ATV.0000114567.76772.33 }}
• {{cite journal | vauthors = Attisano L, Labbé E | title = TGFbeta and Wnt pathway cross-talk | journal = Cancer Metastasis Reviews | volume = 23 | issue = 1–2 | pages = 53–61 | year = 2004 | pmid = 15000149 | doi = 10.1023/A:1025811012690 | s2cid = 41685620 }}
• {{cite journal | vauthors = McGowan TA, Zhu Y, Sharma K | title = Transforming growth factor-beta: a clinical target for the treatment of diabetic nephropathy | journal = Current Diabetes Reports | volume = 4 | issue = 6 | pages = 447–454 | date = Dec 2004 | pmid = 15539010 | doi = 10.1007/s11892-004-0055-z | s2cid = 45122439 }}
• {{cite journal | vauthors = Sheppard D | title = Integrin-mediated activation of latent transforming growth factor beta | journal = Cancer Metastasis Reviews | volume = 24 | issue = 3 | pages = 395–402 | date = Sep 2005 | pmid = 16258727 | doi = 10.1007/s10555-005-5131-6 | s2cid = 1929903 }}
• {{cite journal | vauthors = Gressner AM, Weiskirchen R | title = Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets | journal = Journal of Cellular and Molecular Medicine | volume = 10 | issue = 1 | pages = 76–99 | year = 2006 | pmid = 16563223 | pmc = 3933103 | doi = 10.1111/j.1582-4934.2006.tb00292.x }}
• {{cite journal | vauthors = Seoane J | title = Escaping from the TGFbeta anti-proliferative control | journal = Carcinogenesis | volume = 27 | issue = 11 | pages = 2148–2156 | date = Nov 2006 | pmid = 16698802 | doi = 10.1093/carcin/bgl068 | doi-access = free }}
• {{cite journal | vauthors = Lee CG, Kang HR, Homer RJ, Chupp G, Elias JA | title = Transgenic modeling of transforming growth factor-beta(1): role of apoptosis in fibrosis and alveolar remodeling | journal = Proceedings of the American Thoracic Society | volume = 3 | issue = 5 | pages = 418–423 | date = Jul 2006 | pmid = 16799085 | pmc = 2658706 | doi = 10.1513/pats.200602-017AW }}
• {{cite journal | vauthors = Wahl SM | title = Transforming growth factor-beta: innately bipolar | journal = Current Opinion in Immunology | volume = 19 | issue = 1 | pages = 55–62 | date = Feb 2007 | pmid = 17137775 | doi = 10.1016/j.coi.2006.11.008 | url = https://zenodo.org/record/1258845 }}
• {{cite journal | vauthors = Redondo S, Santos-Gallego CG, Tejerina T | title = TGF-beta1: a novel target for cardiovascular pharmacology | journal = Cytokine & Growth Factor Reviews | volume = 18 | issue = 3–4 | pages = 279–286 | year = 2007 | pmid = 17485238 | doi = 10.1016/j.cytogfr.2007.04.005 }}
• {{cite journal | vauthors = Ren H, Han R, Chen X, Liu X, Wan J, Wang L, Yang X, Wang J | title = Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update | journal = Journal of Cerebral Blood Flow and Metabolism| volume = 40 | issue = 9 | pages = 1752–1768 | date = May 2020 | pmid = 32423330 | pmc = 7446569 | doi = 10.1177/0271678X20923551 | s2cid = 218689863 }}

{{Refend}}

• {{PDBe-KB2|P01137|Transforming growth factor beta-1}}

{{PDB Gallery|geneid=7040}}

{{TGF beta signaling}}

{{Growth factors}}

{{TGFβ receptor superfamily modulators}}

Category:Proteins

Category:TGFβ domain