Summary of TGFB1
TGF-beta plays an important role in autoimmune diseases, food intolerances, cancer, cognitive function, wound healing and other diseases.
TGF-b is a cytokine that affects the growth and proliferation of many cell types, and it has pro- and anti-inflammatory effects. Summary of Activities of TGF-beta:
- Causes collateral damage in infections
- Causes the growth/changes in tissue
- Decreased acetylcholine
- Decreased slow wave or deep sleep
- Decreases muscle regeneration
- Decreases the action of the vitamin D receptor
- Increases free radicals
- Can decrease bone density
- It inhibits proliferation of most other cell types
- Suppresses red blood cell formation and lymphocytes (T and B cells)
- Suppresses antibody production
- Suppresses Cytotoxic T Cell (CD8) and Natural Killer cell activity...this can cause viral infections to get out of control.
- Deactivates macrophages
- Promotes oral tolerance
- Suppresses inflammation
- Promotes wound healing and new blood vessel formation (angiogenesis)
- Induces local inflammation and fibrosis
- Stimulates extracellular matrix deposition
- Promotes switch to IgA
- Can increase cancer growth
- Cause negative changes in the airways
- Can benefit cognitive function (when very mildly elevated)
The Function of TGFB1
Multifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner. At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development. At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells. Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus (PubMed:25893292). Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (PubMed:25893292).
Protein names
Recommended name:
Transforming growth factor beta-1Short name:
LAPAlternative name(s):
TGF-beta-1- RS1800469 (TGFB1) ??
- RS1800470 (TGFB1) ??
- RS1800471 (TGFB1) ??
- RS1800472 (TGFB1) ??
- RS2241715 (TGFB1) ??
- RS4803455 (TGFB1) ??
- RS8110090 (TGFB1) ??
To see your genotype, you should be logged in and have a file with your genotype uploaded.
Top Gene-Substance Interactions
TGFB1 Interacts with These Diseases
Disease | Score |
Fixes
TGF-beta Inhibitors
If you have genes that cause high TGF-beta, you might do better with TGF inhibitors. These inhibit TGF in different places, but not necessarily systemically....
- Sun/UV (R, R2) - at least in skin cells.
- Curcumin (R),
- Black Cumin Seed Oil /Thymoquinone (R) -in rat model of allergic airway inflammation,
- Andrographis/Andrographolide (R),
- Extra Virgin Olive Oil (R),
Fixes Advanced
TGF increases ROS, but Butyrate helps prevent this. (R)
If you have systemically high TGF, you might want to take a mito antioxidant such as MitoQ, since much of the damage from TGF is by increasing ROS in your mitochondria. (R, R2)
Other TGF-beta Inhibitors
If you have genes that cause high TGF-beta, you might do better with TGF inhibitors. These inhibit TGF in different places, but not necessarily systemically....
- PPAR agonists (gamma and alpha) (R, R2, R3, R4) - reduces TGF in blood vessels and the negative effects of TGF in skin, heart muscle and liver cells... PPAR gamma can be considered anti-TGF overall.
- Vitamin D Receptor activation (R), Angiotensin II type 1 receptor antagonist (R)
- Klotho - Specifically, Klotho was shown to bind to the TGF-²1 receptor to inhibit TGF-²1 binding (R).
- Ursolic acid (R),
- Reishi (R),
- Fucoidan (R),
- Resveratrol
(R),
- Apigenin
(R),
- Berberine
(R),
- Quercetin
(R),
- Grape Seed Extract (R),
- Ginkgo (R),
- Pregnenolone (R)
- Astragalus (R, R2),
- Zinc
,
- Silymarin
/Silibinin,
- Hesperidin,
- Garlic,
- Gotu Kola /Asiatic Acid,
- Emodin (found in Fo-Ti, Resveratrol, Rhubarb, Aloe),
- Theanine (R),
- Naringenin,
- Ginseng (R),
- Kudzu root/Puerarin,
- Angelica S, Hydrangea, Dan Shen, Almond, Cordyceps, Butein, Betulinic acid,
- Enterococcus faecalis (R)****,
TGF-beta Increasers
You want to be careful about the following if you have genes that cause higher TGF-beta.
- Hypoxia (R) or low oxygen
- SIRT1 (R) - maybe resveratrol is not a great idea
- Pregnenolone (R), - increases Th2 dominance...
- Estrogen (R) - increased TGF in skin
- T3 (R)
- Progesterone (R, R2) - increased TGF in epithelial cells...which are all over the body...
- S Boulardii (R) - TGF increased in the blood in chicks.
- Bacillus Subtilis (R) - TGF increased in the blood in chicks.
- Artemisinin (R) - increased TGF in spleen cells,
- AngiotensinII- increased TGF in heart (R),
- Beta-2 Adrenoreceptor (R) agonism, increased TGF in the hippocampus...
Substances That Increase TGFB1
Substances | Interaction | Organism | Category |
Substances That Decrease TGFB1
Substances | Interaction | Organism | Category |
Advanced Summary
Read/FIX: TGF Beta: What It Does And Natural Ways to Inhibit and Increase It TGF-beta is produced in cells such as platelets, macrophages, B- and T-lymphocytes, fibroblasts, ECs, osteoblasts and osteoclasts, astrocytes, and microglial cells.
The thymus, bone marrow and bone also produce TGF . There are different types of TGF, but TGF-b1 is the main one involved in immunity.
TGF-beta is often very elevated in people with biotoxin/mold issues. Blood TGF is highly significantly correlated with the platelet count, probably because most of the TGF is released by platelets. (R) You want TGF to be balanced rather than too high or too low...
The Good (Sometimes)
TGF increases serotonin transporters and serotonin uptake in the gut, which is low in IBS and IBD. (R) So this suggests that TGF is protective against autoimmune gut disorders. TGF is increased by helminthic therapy and this is one important mechanism by which it's protective against colitis. (R)
Studies have shown that TGF-b in the gut area is necessary to create tolerance orally. (R)
The primary mechanisms of oral tolerance are the active suppression of immune responses through the induction of regulatory T cells in the gut-associated lymphoid tissue. These Th3 cells secrete TGF-b, IL-4, and IL-10, which decrease Th1 and other immune cells.
TGF-b also leads to the death of T cells that attack our tissue (clonal deletion). (R)
Due to its potent anti-proliferative effects, TGF-b normally functions as a tumor suppressor. However, cancer cells develop resistance to TGF-b late in tumor progression by using multiple mechanisms.
TGF-b promotes wound healing due to its unique effect on the extracellular matrix by stimulating the synthesis of matrix proteins and decreased matrix degradation.
In infections, it protects against collateral damages caused by the immune system, but it also promotes immune evasion by pathogens and therefore can lead to chronic infections.
TGF-b suppresses the immune system at the systemic level but stimulates the immune and inflammatory responses at the local level.
TGF-b1 deficient mice develop an inflammatory response with massive white blood cell infiltration in numerous organs, accompanied by increased expression of TNF-a, IFN-g, and class I and II MHC antigens, resulting in death at 3 to 5 weeks.
These mice also have high levels of autoantibodies. Thus, TGF-b1 normally acts as an active suppressor of inflammation. TGF-b can suppress the proliferation of T- and B-lymphocytes, monocytes, and macrophages.
It suppresses immunoglobulin (Ig) secretion of mature B cells, but can increase IgA production (not a cause of autoimmunity). TGF-b inhibits IFN-g, IL-2, IL-3, GM-CSF, and TNF-a in response to infections or other stimuli.
TGF-b also decreases E-selectin and IL-8 on blood vessels. TGF-b can deactivate macrophages by reducing their capacity to release superoxide and nitric oxide, suppressing their cytotoxic activity, decreasing their expression of MHC class II, inhibiting the production of TNF-a and IL-1, and antagonizing the effects of these cytokines.
TGF-b can also benefit cognitive function. One study found TGF-beta was associated with increased cortical thickness, and this is thought in part to do with the reduction of cytokines. (R) TGF is low in advanced atherosclerosis.
The Bad
TGF-b can increase inflammation locally. TGF-b inhibits acetylcholine formation (in muscle and spinal cells) (R). Inhibition of acetylcholine formation elegantly explains many of the symptoms that CIRS people have (R). In an inflammatory environment, it will produce proinflammatory Th17 and Th9 cells (instead of Tregs) and inhibit Th22 cells. (R)
TGF-b suppresses red blood cells by inhibiting bone marrow stem-cell proliferation and decreasing the expression of receptors for SCF400, IL-3, and GM-CSF in hematopoietic cells (R).
One thing that is interesting is that I have a client/friend with high TGF and low RBCs. This makes sense because TGF decreases RBC formation.
In cancer, TGF-² is a potent inhibitor of cell proliferation and acts as a tumor suppressor at the beginning of tumor formation. However, once the cells become resistant to TGF-², it mainly supports tumor growth and metastasis by promoting immune evasion and angiogenesis. (R)
TGFbeta decreases slow wave sleep (R, R2). TGF-b decreases muscle regeneration (R), which is one reason why people with CIRS lose muscle. TGF-b will increase VEGF , by increasing hypoxia inducible factor, which can make tumors spread. (R, R2)
Indeed, an elevated blood level of TGF-b significantly correlated with lymph node metastasis and poor prognosis in patients with gastric cancer. (R) TGF-beta decreases the action of the vitamin D receptor (R).
In asthma, TGF-b is assumed to promote allergen tolerance, but plays a detrimental role in irreversible tissue changes of the airways. (R)
TGF-b causes various cells to stick to the site of inflammation and tissue injury (chemotaxis). These include neutrophils, monocytes, lymphocytes, mast cells, and fibroblasts; TGF-beta also activates these cells to produce inflammatory cytokines (IL-1, TNF, and IL-6); and causes white blood cells to stick to the vessel wall and Extracellular matrix.
TGF-b secretion is increased by male hormone treatment in certain hair cells. Androgens increase ROS, which increases TGF . (R) TGF-b has both positive and negative effects on bone mineral density.
It's thought by scientists that in the short term in can help bone density, but chronically elevated TGF-b will decrease bone density. (R)
TGF-b has been proposed as a contributing factor in many chronic inflammatory diseases, which include rheumatoid arthritis, glomerulonephritis, pulmonary fibrosis, systemic sclerosis, and chronic hepatitis.
TGF-b is elevated in the blood of patients with invasive prostate cancer.
Camurati-Engelmann disease Approximately 10 mutations in the TGFB1 gene have been found to cause Camurati-Engelmann disease. Most of the mutations change one protein building block (amino acid) in the TGFβ-1 protein. The most common mutation replaces the amino acid arginine with the amino acid cysteine at position 218 in the TGFβ-1 protein (written as Arg218Cys or R218C). All mutations that cause Camurati-Engelmann disease result in a TGFβ-1 protein that is always turned on (active). The overactive protein likely disrupts the regulation of bone growth and impairs muscle and body fat development. A disruption in the regulation of TGFβ-1 activity can lead to increased bone density and other features of Camurati-Engelmann disease. cancers Some TGFB1 gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes are called somatic mutations and are not inherited. Somatic mutations in the TGFB1 gene that cause alterations in the activity (expression) of the TGFβ-1 protein are associated with certain cancers. The altered protein expression may enhance several cancer-related events such as cell division (proliferation), cell motility, and the development of new blood vessels (angiogenesis) that nourish a growing tumor. The TGFβ-1 protein is abnormally active (overexpressed) in certain types of prostate cancers. Altered TGFβ-1 expression has also been found in breast, colon, lung, and bladder cancers. A variation (polymorphism) in the TGFB1 gene that changes a single amino acid in the TGFβ-1 protein is associated with prostate cancer. In people with this polymorphism, the amino acid leucine is replaced with the amino acid proline at position 10 in the TGFβ-1 protein. Although it has no apparent effect in healthy people or those with a condition caused by a different mutation in the TGFB1 gene, this polymorphism is associated with accelerated disease progression and a poorer outcome in patients with prostate cancer.
The TGFB1 gene provides instructions for producing a protein called transforming growth factor beta-1 (TGFβ-1). The TGFβ-1 protein helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (motility), and the self-destruction of cells (apoptosis). The TGFβ-1 protein is found throughout the body and plays a role in development before birth, the formation of blood vessels, the regulation of muscle tissue and body fat development, wound healing, and immune system function. TGFβ-1 is particularly abundant in tissues that make up the skeleton, where it helps regulate bone growth, and in the intricate lattice that forms in the spaces between cells (the extracellular matrix). Within cells, this protein is turned off (inactive) until it receives a chemical signal to become active.
Conditions with Increased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Highly expressed in bone. Abundantly expressed in articular cartilage and chondrocytes and is increased in osteoarthritis (OA). Colocalizes with ASPN in chondrocytes within OA lesions of articular cartilage.
Gene Pathways:
- Rheumatoid arthritis
- Hemostasis
- Cytokine-cytokine receptor interaction
- Chagas disease (American trypanosomiasis)
- Tuberculosis
- Toxoplasmosis
- Pathways in cancer
- Leishmaniasis
- Intestinal immune network for IgA production
- Hypertrophic cardiomyopathy (HCM)
- Disease
- Dilated cardiomyopathy
- Osteoclast differentiation
- Malaria
- Colorectal cancer
- Amoebiasis
- MAPK signaling pathway
- Signal Transduction
- Chronic myeloid leukemia
- TGF-beta signaling pathway
- Pancreatic cancer
- Renal cell carcinoma
- Extracellular matrix organization
Induction:
Activated in vitro at pH below 3.5 and over 12.5.
Molecular Function:
- Glycoprotein Binding
- Antigen Binding
- Type Ii Transforming Growth Factor Beta Receptor Binding
- Cytokine Activity
- Transforming Growth Factor Beta Receptor Binding
- Enzyme Binding
- Type I Transforming Growth Factor Beta Receptor Binding
- Type Iii Transforming Growth Factor Beta Receptor Binding
- Protein Serine/Threonine Kinase Activator Activity
Biological Processes:
- Protein Import Into Nucleus, Translocation
- Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
- Mapk Cascade
- Vasculogenesis
- Ureteric Bud Development
- Response To Hypoxia
- Epithelial To Mesenchymal Transition
- Neural Tube Closure
- Negative Regulation Of Protein Phosphorylation
- Positive Regulation Of Protein Phosphorylation
- Regulation Of Sodium Ion Transport
- Chondrocyte Differentiation
- Hematopoietic Progenitor Cell Differentiation
- Connective Tissue Replacement Involved In Inflammatory Response Wound Healing
- Adaptive Immune Response Based On Somatic Recombination Of Immune Receptors Built From Immunoglobulin Superfamily Domains
- Tolerance Induction To Self Antigen
- Platelet Degranulation
- Heart Valve Morphogenesis
- Protein Phosphorylation
- Protein Export From Nucleus
- Atp Biosynthetic Process
- Phosphate-Containing Compound Metabolic Process
- Cellular Calcium Ion Homeostasis
- Inflammatory Response
- Smad Protein Complex Assembly
- Cell Cycle Arrest
- Smad Protein Import Into Nucleus
- Mitotic Cell Cycle Checkpoint
- Epidermal Growth Factor Receptor Signaling Pathway
- Transforming Growth Factor Beta Receptor Signaling Pathway
- Common-Partner Smad Protein Phosphorylation
- Notch Signaling Pathway
- Negative Regulation Of Neuroblast Proliferation
- Salivary Gland Morphogenesis
- Endoderm Development
- Heart Development
- Female Pregnancy
- Aging
- Negative Regulation Of Dna Replication
- Positive Regulation Of Cell Proliferation
- Negative Regulation Of Cell Proliferation
- Germ Cell Migration
- Response To Radiation
- Response To Wounding
- Response To Glucose
- Defense Response To Fungus, Incompatible Interaction
- Positive Regulation Of Vascular Endothelial Growth Factor Production
- Positive Regulation Of Gene Expression
- Negative Regulation Of Gene Expression
- Negative Regulation Of Extracellular Matrix Disassembly
- Positive Regulation Of Epithelial To Mesenchymal Transition
- Macrophage Derived Foam Cell Differentiation
- Positive Regulation Of Fibroblast Migration
- Positive Regulation Of Peptidyl-Threonine Phosphorylation
- Positive Regulation Of Pathway-Restricted Smad Protein Phosphorylation
- Negative Regulation Of Macrophage Cytokine Production
- Oligodendrocyte Development
- Cell Growth
- Regulation Of Striated Muscle Tissue Development
- Regulation Of Transforming Growth Factor Beta Receptor Signaling Pathway
- Evasion Or Tolerance Of Host Defenses By Virus
- Neural Tube Development
- Negative Regulation Of Cell-Cell Adhesion
- Hyaluronan Catabolic Process
- Negative Regulation Of Ossification
- Negative Regulation Of Cell Growth
- Regulation Of Cell Migration
- Positive Regulation Of Cell Migration
- Positive Regulation Of Bone Mineralization
- Negative Regulation Of Transforming Growth Factor Beta Receptor Signaling Pathway
- Positive Regulation Of Histone Deacetylation
- Membrane Protein Intracellular Domain Proteolysis
- Positive Regulation Of Exit From Mitosis
- Lipopolysaccharide-Mediated Signaling Pathway
- Positive Regulation Of Cellular Protein Metabolic Process
- Response To Estradiol
- Response To Progesterone
- Regulation Of Interleukin-23 Production
- Negative Regulation Of Interleukin-17 Production
- Positive Regulation Of Interleukin-17 Production
- Receptor Catabolic Process
- Positive Regulation Of Superoxide Anion Generation
- Mononuclear Cell Proliferation
- Positive Regulation Of Collagen Biosynthetic Process
- Positive Regulation Of Peptidyl-Serine Phosphorylation
- Response To Vitamin D
- Response To Laminar Fluid Shear Stress
- Positive Regulation Of Histone Acetylation
- Positive Regulation Of Protein Dephosphorylation
- Response To Immobilization Stress
- Negative Regulation Of T Cell Proliferation
- Regulation Of Protein Import Into Nucleus
- Positive Regulation Of Protein Import Into Nucleus
- Positive Regulation Of Odontogenesis
- Myelination
- Regulation Of Apoptotic Process
- Myeloid Dendritic Cell Differentiation
- T Cell Homeostasis
- Positive Regulation Of Apoptotic Process
- Positive Regulation Of Vascular Permeability
- Positive Regulation Of Map Kinase Activity
- Protein Kinase B Signaling
- Positive Regulation Of Blood Vessel Endothelial Cell Migration
- Negative Regulation Of Blood Vessel Endothelial Cell Migration
- Positive Regulation Of Phosphatidylinositol 3-Kinase Activity
- Ossification Involved In Bone Remodeling
- Regulatory T Cell Differentiation
- Cell-Cell Junction Organization
- Positive Regulation Of Regulatory T Cell Differentiation
- Negative Regulation Of Cell Differentiation
- Negative Regulation Of Fat Cell Differentiation
- Negative Regulation Of Myoblast Differentiation
- Negative Regulation Of Cell Cycle
- Negative Regulation Of Transcription, Dna-Templated
- Positive Regulation Of Transcription, Dna-Templated
- Negative Regulation Of Mitotic Cell Cycle
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Active Induction Of Host Immune Response By Virus
- Positive Regulation Of Fibroblast Proliferation
- Positive Regulation Of Isotype Switching To Iga Isotypes
- Lymph Node Development
- Digestive Tract Development
- Negative Regulation Of Skeletal Muscle Tissue Development
- Inner Ear Development
- Positive Regulation Of Epithelial Cell Proliferation
- Negative Regulation Of Epithelial Cell Proliferation
- Positive Regulation Of Protein Secretion
- Positive Regulation Of Peptidyl-Tyrosine Phosphorylation
- Negative Regulation Of Phagocytosis
- Positive Regulation Of Chemotaxis
- Positive Regulation Of Nf-Kappab Transcription Factor Activity
- Regulation Of Binding
- Regulation Of Dna Binding
- Positive Regulation Of Smooth Muscle Cell Differentiation
- Negative Regulation Of Release Of Sequestered Calcium Ion Into Cytosol
- Positive Regulation Of Cell Division
- Positive Regulation Of Protein Kinase B Signaling
- Ventricular Cardiac Muscle Tissue Morphogenesis
- Regulation Of Blood Vessel Remodeling
- Face Morphogenesis
- Frontal Suture Morphogenesis
- Pathway-Restricted Smad Protein Phosphorylation
- Regulation Of Smad Protein Import Into Nucleus
- Positive Regulation Of Smad Protein Import Into Nucleus
- Smad Protein Signal Transduction
- Mammary Gland Branching Involved In Thelarche
- Branch Elongation Involved In Mammary Gland Duct Branching
- Regulation Of Branching Involved In Mammary Gland Duct Morphogenesis
- Negative Regulation Of Gene Silencing By Mirna
- Regulation Of Cartilage Development
- Lens Fiber Cell Differentiation
- Positive Regulation Of Erk1 And Erk2 Cascade
- Response To Cholesterol
- Positive Regulation Of Cell Cycle Arrest
- Cellular Response To Mechanical Stimulus
- Cellular Response To Organic Cyclic Compound
- Cellular Response To Ionizing Radiation
- Cellular Response To Dexamethasone Stimulus
- Cellular Response To Transforming Growth Factor Beta Stimulus
- Positive Regulation Of Mononuclear Cell Migration
- Extracellular Matrix Assembly
- Positive Regulation Of Branching Involved In Ureteric Bud Morphogenesis
- Extrinsic Apoptotic Signaling Pathway
- Liver Regeneration
- Negative Regulation Of Hyaluronan Biosynthetic Process
- Positive Regulation Of Extracellular Matrix Assembly
- Positive Regulation Of Nad+ Adp-Ribosyltransferase Activity
- Positive Regulation Of Pri-Mirna Transcription From Rna Polymerase Ii Promoter
- Negative Regulation Of Protein Localization To Plasma Membrane
- Positive Regulation Of Receptor Clustering
- Negative Regulation Of Production Of Mirnas Involved In Gene Silencing By Mirna
- Transforming Growth Factor Beta Receptor Signaling Pathway Involved In Heart Development
- Cellular Response To Insulin-Like Growth Factor Stimulus
- Embryonic Liver Development
- Regulation Of Actin Cytoskeleton Reorganization
- Positive Regulation Of Transcription Regulatory Region Dna Binding
- Positive Regulation Of Cardiac Muscle Cell Differentiation
Drug Bank:
- Hyaluronidase
- Hyaluronidase (Human Recombinant)