TB4 including its role as an actin sequestrant and its roles in inflammation and immune function.
Thymosin Beta-4, or TB4, sometimes called TB500, is a 44-amino-acid peptide and signaling protein with divergent functions throughout the body. TB4 is found in nearly all types of living tissue. Initially discovered in its role as an actin-sequestration agent, TB4 is now understood in humans and animal models to play a role in wound-healing, neurological regeneration, cardiac regeneration, immune function, cell migration, and blood vessel formation.
Thymosins interact with actin and regulate its growth and function and thereby the growth and function of both smooth and skeletal muscle-tissue; thymosin beta-4 binds with G-actin (a monomeric or single-strand form of actin) and stabilizes it; along with ATP and another monomeric filament, this complex forms F-actin, the polymeric thin filament found in muscle tissue. It is in this way that TB4 plays a key role in tissue regeneration, vascularization, and wound repair.
The ways thymosin beta-4 interacts with actin in different types of tissue is not limited to pure regulation of growth in contractile and smooth tissue:
After injury, thymosin B(4), is released by platelets, macrophages and many other cell types to protect cells and tissues from further damage and reduce apoptosis, inflammation and microbial growth. Thymosin B(4) binds to actin and promotes cell migration, including the mobilization, migration, and differentiation of stem/progenitor cells, which form new blood vessels and regenerate the tissue. Thymosin B(4) also decreases the number of myofibroblasts in wounds, resulting in decreased scar formation and fibrosis.[1]
TB4 has several moonlighting roles, such as modulation of inflammation in different types of tissue, and indirect (as opposed to direct via chemotaxis) influence on immune function.
Thymosin beta 4 is largely unfolded or perhaps completely unfolded in solution. Based on the paradigm introduced by Wright and Dyson that unfolded proteins may have multiple functions based on their ability to recognize numerous ligands, the flexible structure of thymosin beta 4 may facilitate the recognition of a variety of molecular targets, thus explaining the plethora of functions attributed to thymosin beta 4. Furthermore, if multiple ligands bind to thymosin beta 4, then it is possible that thymosin beta 4 has a unique integrative function that links the actin cytoskeleton to important immune and cell growth-signaling cascades. [3,4]
Thymosin beta-4 is a potent wound healing accelerator, and many of the current (experimental) clinical uses focus on its ability to speed healing in disease states. In addition to its promising effects in inflammatory and immune disorders, TB4 has been shown to be beneficial and important in targeted tissue regeneration in disease states such as advanced diabetes mellitus as stated by Treadwell
naturally occurring, endogenous repair molecule, thymosin beta 4 (TB4), has many biological activities that promote dermal repair. It is released by platelets at the site of injury and initiates the repair cascade. TB4 accelerated dermal healing
TB4 likely acts to repair and regenerate wounds by promoting cell migration and stem cell mobilization and differentiation, and by inhibiting inflammation, apoptosis, and infection. We conclude that TB4 is a multifunctional regenerative peptide important in dermal repair.[5]
The ability of exogenous TB4 to reduce fibrotic tissue formation, reduce damage from ischemia/reperfusion, and accelerate wound-healing …
[1]Goldstein AL, Hannappel E, Sosne G, Kleinman HK. Thymosin ?4: a multi-functional regenerative peptide. Basic properties and clinical applications. Expert Opin Biol Ther. 2012 Jan;12(1):37-51.
[3]Wright PE, Dyson HJ. .Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J Mol Biol. 1999 Oct 22;293(2):321-31
[4]Bubb MR. Thymosin beta 4 interactions. Vitam Horm. 2003;66:297-316.
[5]Treadwell T, Kleinman HK, Crockford D, Hardy MA, Guarnera GT, Goldstein AL. The regenerative peptide thymosin ?4 accelerates the rate of dermal healing in preclinical animal models and in patients. Ann N Y Acad Sci. 2012 Oct;1270:37-44.