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Transforming growth factor beta TGF beta - Biotech, Pharma and Life Science Channel

01:58 EDT 19th July 2018 | BioPortfolio

Transforming growth factor-beta (TGF-beta) family members are secreted multifunctional cytokines that play pivotal roles in development and disease. The prototypic member of this family, TGF-beta, plays a dual role in carcinogenesis, acting as a tumor suppressor in early stages and as tumor promoter in late stages of tumor progression. Aberrant TGF-beta expression is implicated in the pathogenesis of fibrosis in systemic sclerosis; thus, TGF-beta represents a molecular therapeutic target in this disease. Small-molecule inhibitors of TGF-beta-receptor activity are effective in animal models of fibrosis. TGF-beta1 is believed to play an important role in wound healing and repair, as it is a key regulator of the production and remodelling of the extracellular matrix through its effect on mesenchymal cells. Over the last few years, it has become evident that the signalling pathway of TGF-beta is complex with numerous receptor-ligand interactions, intracellular pathways and a number of mechanisms, which not only control the signalling but may also decide the response to the TGFbeta signal.

TGF and its receptor are targets for agonists and antagonists which are under development in a variety of diseases ranging from prevention of scarring and osteoarthritis to cancer (e.g., NSCLC; astrocytoma, melanoma, pancreatic cancer) and scleroderma, chronic kidney disease - glomerulosclerosis. Most of the molecules are biologics (antibodies, proteins, peptides, antisense, vaccine, cells). The most advanced projects are in phase III development.

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Medical and Biotech [MESH] Definitions

Cell-surface proteins that bind transforming growth factor beta and trigger changes influencing the behavior of cells. Two types of transforming growth factor receptors have been recognized. They differ in affinity for different members of the transforming growth factor beta family and in cellular mechanisms of action.

Hormonally active polypeptides that can induce the transformed phenotype when added to normal, non-transformed cells. They have been found in culture fluids from retrovirally transformed cells and in tumor-derived cells as well as in non-neoplastic sources. Their transforming activities are due to the simultaneous action of two otherwise unrelated factors, TRANSFORMING GROWTH FACTOR ALPHA and TRANSFORMING GROWTH FACTOR BETA.

A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.

A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.

A large family of cell regulatory proteins which are structurally related to TRANSFORMING GROWTH FACTOR BETA. The superfamily is subdivided into at least three related protein families: BONE MORPHOGENETIC PROTEINS; GROWTH DIFFERENTIATION FACTORS; and TRANSFORMING GROWTH FACTORS.

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