TGFB1

The TGFB1 gene codes for transforming growth factor beta 1 (TGF-beta1). 

TGF-beta1 is an immune messenger (cytokine) that plays a role in many cellular processes, including [R]: 

• Cell growth and division (cell proliferation)
• Cell specialization
• Cell movement
• Cell death

These processes may influence [R]:

• Bone and cartilage formation
• Blood vessel formation
• Muscle and fat development
• Wound healing
• Inflammation
• Tumor suppression 

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.

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.

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),