Functions of TGF B-1:
Quick facts:
- TGF B-1 regulates immune and tissue cell growth and proliferation.
- TGF B-1 is involved in maintenance of tissue homeostasis.
- TGF B-1 helps regulate effects in the innate immune system.
- TGF B-1 is an immune suppressor (although it can upregulate the immune system in some instances)
The TGFβs are involved in many cellular processes, including growth inhibition, cell migration, invasion, epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) remodeling and immune-suppression. However, although normally dynamically regulated and involved in maintenance of tissue homeostasis, TGFβs are often chronically over-expressed in disease states, including cancer, fibrosis and inflammation, and this excessive production of TGFβ drives disease progression by modulating cell growth, migration or phenotype. The TGFβ signalling pathway has therefore become a popular target for drug development.
Disruption of the TGF-β pathway has been implicated in many human diseases, including solid and hematopoietic tumors. As a potent inhibitor of cell proliferation, TGF-β acts as a tumor suppressor; however in tumor cells, TGF-β loses anti-proliferative response and becomes an oncogenic factor.
The TGFB family of cytokines consists of the following:
The transforming growth factor (TGF-β) family of growth factors controls an immense number of cellular responses and figures prominently in development and homeostasis of most human tissues.
- TGFβs,
- activins,
- inhibins,
- Nodal,
- bone morphogenetic proteins (BMPs),
- anti-Müllerian hormone (AMH; also known as Müllerian-inhibiting factor)
- as well as growth and differentiation factors (GDFs)
Research shows that TGF B-1 has a role in activation of autoimmunity as well as suppressing autoimmunity. TGF-beta, together with IL-6 and IL-21, promotes Th17 cell development. Th17 cells have been identified as a lineage distinct from Th1 and Th2 cells, and are required for induction of several autoimmune diseases, including collagen-induced arthritis, experimental autoimmune encephalitis (EAE), and inflammatory bowel disease (IBD), and also for the ability to clear bacterial infections of the intestine and the airways.
It appears TGF beta-1 is not immune suppressive if T-reg cells (known by their CD4+/CD25+ cell surface markers) are in normal range. If T-regs are low, TGF- beta 1 can transform them into pathogenic T-cells in tissues, as happens in CIRS cases. This transformation may depend in part on IL-6. The net result is a positive feedback loop in which more TGF-beta gets produced.
TGF-β as a tumor promoter:
TGF-β acts as tumor suppressor in normal epithelium; it inhibits cell proliferation and induces apoptosis. Yet, during tumor progression, sensitivity to these effects of TGF-β is frequently lost and, in later stages, TGF-β signaling has pro-oncogenic function. Several activities have been described to TGF-β that would favor tumor progression [L].
Other references:
https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-10-183
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- TGF B-1 is often chronically over-expressed in disease states, including cancer, fibrosis and inflammation.
- TGF B-1 is moderately to extremely high in Chronic Inflammatory Response Syndrome due to water-damaged buildings (CIRS).
- Prolonged elevations of TGF B-1 levels can create conditions where tissue remodeling and autoimmune transformation become more likely.
- Transforming growth factor-beta 1 (TGF-b1) is a regulatory protein, involved in bone fracture healing. Circulating TGF-b1 levels have been reported to be a predictor of delayed bone healing and non-union, suggesting active relationship between tissue and circulating TGF-b1 in fracture healing. [L]
- High levels of transforming growth factor B1 have been associated with disease progression in patients with colorectal cancer. [L]
- Increased levels of transforming growth factor-beta1 (TGF-B1) have been reported in endometriosis (in animal studies), which is a prevalent gynecological disorder that eventually gives rise to painful invasive lesions. [L]
- A study found that there might be some correlation between Tgf-b1 and prostate cancer. [L]
- Overexpression of TGF-b1 has been reported as a negative predictor in esophageal cancer. [L]
- Increased TGF-b2 in severe asthma with eosinophilia [L]
- Increased transforming growth factor-b1 plasma concentration is associated with high plasma 3,3 0 ,5 0 -tri-iodothyronine in elderly patients with nonthyroidal illnesses. [European Journal of Endocrinology (1998) 138 47–50, Department of Internal Medicine, Division of Internal Medicine and Metabolic Diseases, School of Medicine, University of Messina, Policlinico Universitario, Via Consolare Valeria, I-98124 Messina, Italy]
Some symptoms of high levels could be:
- lung symptoms,
- neurological problems,
- learning disability,
- resting tremors,
- unusual seizures.
- low levels and high levels may both be related to autoimmune disease.
High TGF Beta-1 is further associated with:
- loss of hair,
- sudden onset of inflammatory response
- tinnitus, nystagmus, and hearing loss.
- renal fibrosis.
Lowering TGFb1 enhances neurogenesis and muscle regeneration.
Potential inhibitors of TGF B-1:
- Curcumin [L]
- Black cumin seed oil [L]
- Extra virgin olive oil [L]
- Berberine [L]
- Grape seed extract
- Ginkgo [L]
- Zinc
- Garlic
- Ginseng [L]
- stop smoking if you do [L]
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