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TGF beta 1
Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the transforming growth factor beta superfamily of cytokines. It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation, and apoptosis. In humans, TGF-β1 is encoded by the TGFB1 gene.
Function
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.
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. 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.
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.
T cells
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, as well as the activation of quiescent helper T cells and cytotoxic T cells. 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, particularly if the cells are immature.
B cells
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, and controls the expression of antibody, transferrin and MHC class II proteins on immature and mature B cells.
Myeloid 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.
Interactions
TGF beta 1 has been shown to interact with:
- Decorin,
- EIF3I
- LTBP1,
- TGF beta receptor 1, and
- YWHAE.
Further reading
- Border WA, Noble NA (1994). "Transforming growth factor beta in tissue fibrosis". N. Engl. J. Med. 331 (19): 1286–92. doi:10.1056/NEJM199411103311907. PMID 7935686.
- Munger JS, Harpel JG, Gleizes PE, Mazzieri R, Nunes I, Rifkin DB (1997). "Latent transforming growth factor-beta: structural features and mechanisms of activation". Kidney Int. 51 (5): 1376–82. doi:10.1038/ki.1997.188. PMID 9150447.
- Iozzo RV (1999). "The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins". J. Biol. Chem. 274 (27): 18843–6. doi:10.1074/jbc.274.27.18843. PMID 10383378.
- Reinhold D, Wrenger S, Kähne T, Ansorge S (1999). "HIV-1 Tat: immunosuppression via TGF-beta1 induction". Immunol. Today. 20 (8): 384–5. doi:10.1016/S0167-5699(99)01497-8. PMID 10431160.
- Yamada Y (2001). "Association of polymorphisms of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis". Pharmacogenetics. 11 (9): 765–71. doi:10.1097/00008571-200112000-00004. PMID 11740340.
- Chen W, Wahl SM (2002). "TGF-β: Receptors, Signaling Pathways and Autoimmunity". TGF-beta: receptors, signaling pathways and autoimmunity. Curr. Dir. Autoimmun. Current Directions in Autoimmunity. Vol. 5. pp. 62–91. doi:10.1159/000060548. ISBN 978-3-8055-7308-5. PMID 11826761.
- Marone M, Bonanno G, Rutella S, Leone G, Scambia G, Pierelli L (2002). "Survival and cell cycle control in early hematopoiesis: role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21". Leuk. Lymphoma. 43 (1): 51–7. doi:10.1080/10428190210195. PMID 11908736. S2CID 28490341.
- Schnaper HW, Hayashida T, Hubchak SC, Poncelet AC (2003). "TGF-beta signal transduction and mesangial cell fibrogenesis". Am. J. Physiol. Renal Physiol. 284 (2): F243–52. doi:10.1152/ajprenal.00300.2002. PMID 12529270. S2CID 17046094.
- Kalluri R, Neilson EG (2003). "Epithelial-mesenchymal transition and its implications for fibrosis". J. Clin. Invest. 112 (12): 1776–84. doi:10.1172/JCI20530. PMC 297008. PMID 14679171.
- Grainger DJ (2004). "Transforming growth factor beta and atherosclerosis: so far, so good for the protective cytokine hypothesis". Arterioscler. Thromb. Vasc. Biol. 24 (3): 399–404. doi:10.1161/01.ATV.0000114567.76772.33. PMID 14699019.
- Attisano L, Labbé E (2004). "TGFbeta and Wnt pathway cross-talk". Cancer Metastasis Rev. 23 (1–2): 53–61. doi:10.1023/A:1025811012690. PMID 15000149. S2CID 41685620.
- McGowan TA, Zhu Y, Sharma K (2004). "Transforming growth factor-beta: a clinical target for the treatment of diabetic nephropathy". Curr. Diab. Rep. 4 (6): 447–54. doi:10.1007/s11892-004-0055-z. PMID 15539010. S2CID 45122439.
- Sheppard D (2005). "Integrin-mediated activation of latent transforming growth factor beta". Cancer Metastasis Rev. 24 (3): 395–402. doi:10.1007/s10555-005-5131-6. PMID 16258727. S2CID 1929903.
- Gressner AM, Weiskirchen R (2006). "Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets". J. Cell. Mol. Med. 10 (1): 76–99. doi:10.1111/j.1582-4934.2006.tb00292.x. PMC 3933103. PMID 16563223.
- Seoane J (2006). "Escaping from the TGFbeta anti-proliferative control". Carcinogenesis. 27 (11): 2148–56. doi:10.1093/carcin/bgl068. PMID 16698802.
- Lee CG, Kang HR, Homer RJ, Chupp G, Elias JA (2006). "Transgenic modeling of transforming growth factor-beta(1): role of apoptosis in fibrosis and alveolar remodeling". Proc Am Thorac Soc. 3 (5): 418–23. doi:10.1513/pats.200602-017AW. PMC 2658706. PMID 16799085.
- Wahl SM (2007). "Transforming growth factor-beta: innately bipolar". Curr. Opin. Immunol. 19 (1): 55–62. doi:10.1016/j.coi.2006.11.008. PMID 17137775.
- Redondo S, Santos-Gallego CG, Tejerina T (2007). "TGF-beta1: a novel target for cardiovascular pharmacology". Cytokine Growth Factor Rev. 18 (3–4): 279–86. doi:10.1016/j.cytogfr.2007.04.005. PMID 17485238.
- Ren H, Han R, Chen X, Liu X, Wan J, Wang L, Yang X, Wang J (May 2020). "Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update". J Cereb Blood Flow Metab. 40 (9): 1752–1768. doi:10.1177/0271678X20923551. PMC 7446569. PMID 32423330. S2CID 218689863.
External links
- Overview of all the structural information available in the PDB for UniProt: P01137 (Transforming growth factor beta-1) at the PDBe-KB.
PDB gallery
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TGF beta superfamily of ligands |
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TGF beta receptors (Activin, BMP, family) |
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Fibroblast |
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TGFβ pathway | |||||||||
Insulin/IGF/ Relaxin family |
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Type III |
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Unsorted |
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