TGF- β Signaling Pathways and their Enigmatic Role as a Friend and Foe in Human Health and Diseases

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About this Research Topic

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Background

Humans start their lives as a single embryonic cell and evolve into an adult body consisting of approximately 50 trillion cells, by adopting an intricate and efficient network of signalling pathways to send messages quickly for coordinating the actions of distant organs, tissues, and cells to fine-tune their specific functions. These fundamental cellular signalling pathways are carried out by physical modulators including mechanical pressure, extracellular matrix stiffness, voltage, temperature and light as well as by chemical modulators including growth factors, cytokines, chemokines, and hormones. A well-documented chemical modulator involved in various molecular signalling cascades, is transforming growth factor beta (TGF-β). TGF-β is a secreted cytokine that is present in three main isoforms (TGF-β1, TGF-β2, and TGF-β3). Once synthesised and processed from their precursor form, TGF-β exists as mature homo or heterodimeric ligands. These active dimers play important roles in many cellular processes including cell growth, differentiation, proliferation, migration, apoptosis, cellular homeostasis, and other cellular functions.

TGF- β activates a number of Smad-dependent and independent signalling pathways, including BMP, CSF-1, RANKL/RANK, TRAF6, NF-kB, AP-1, Notch, Ras/MAPK, PI 3-K/Akt, p38, JNK, and Rho A/ROCK. Activation of these pathways may also contribute to the cellular responses induced by TGF-beta. TGF-β-associated signalling pathways are often subjected to aberrant disruptions and are known to function as a double-edged sword to human health and disease development. TGF-β activates a number of cellular receptors, and alterations of active TGF-β levels is linked to the dysregulation of its signalling pathways leading to tissue injury and cancer. TGF-β signalling is well recognized for its pleiotropic action as both a tumour suppressor and a promotor in cancers, as well as having a direct influence on disease progression in various conditions such as fibrosis, hypertension, and atherosclerosis. As such, there is a global desire to elucidate the numerous molecular players and their interactions in TGF-β signalling and to precisely understand their role in various cellular processes, which may lead to the discovery of new therapeutic interventions in cancer, fibrosis, Marfan syndrome, Osler-Weber-Rendu syndrome, CCM, HHT, CARASIL, osteoporosis, glaucoma, glomerulosclerosis, diabetic kidney disease, cerebrovascular disease, and many other human diseases.

This Research Topic welcomes original research, reviews, and other article types, investigating TGF-β signalling, which may contribute to the development of novel and effective therapeutic options to treat cancer and other human diseases.

Keywords: TGF-B, Signaling, Growth Factor, Protein, Pathways

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