TB-500 (Thymosin Beta-4)

What is TB-500 (Thymosin Beta-4)?

TB-500 is a derivative of the protein named Thymosin Beta-4, which is a small, 5-kDa protein with a diverse spectrum of activities, including its function as an anti-inflammatory agent, an actin monomer sequestering protein and an inhibitor of bone marrow stem cell proliferation. Only the effects of Thymosin Beta-4 on the actin cytoskeleton have an explanation based on identified molecular interactions. 

Studies suggest that TB-500 has the ability to promote healing and tissue regeneration, and it was actually first used to increase muscle growth and tissue repair in horses and other mammals.

Thymosin Beta-4 is largely unfolded or perhaps completely unfolded in solution. Based on the Wright and Dyson paradigm - "unfolded proteins may have multiple functions due to their ability to recognize numerous ligands", the flexible structure of TB-500 may facilitate the recognition of a variety of molecular targets, thus explaining the plethora of functions attributed to TB-500 peptide. Furthermore, if multiple ligands bind to this peptide, they may have a unique integrative function that links the actin cytoskeleton to significant immune and cell growth-signaling cascades.

TB-500 Research Benefits

TB-500 Regulation of Actin in Sepsis Research

Sepsis is the dysregulated host response to an infection resulting in life-threatening organ damage. TB-500 is an actin-binding protein that inhibits the polymerization of G-actin into F-actin and improves mortality when administered intravenously to septic rats. 

Furthermore, Thymosin Beta-4 decreases inflammatory mediators, lowers reactive oxygen species, and up-regulates anti-oxidative enzymes, anti-inflammatory genes, and anti-apoptotic enzymes making it an interesting protein to study in sepsis.

TB-500 Peptide and Acute Wounds Research

Back in 1999, a research study was conducted on wounded murine test models administered with TB-500.

Four days later, researchers noticed that the TB-500 peptide rats experienced an alleged 41% increase in re-epithelialization compared with control murine models administered with saline. After seven days, a study has shown that the TB-500 wounds were contracted by at least 11% more than the saline wounds. 

Overall results of this study showed that TB-500 may possibly induce angiogenesis and collagen deposition, improving wound healing rate.

Thymosin Beta-4 as a Part of Dry Eye Therapy

Thymosin Beta-4 has essential applications in ocular repair, and phase 3 clinical trials using this peptide to treat dry eye and neurotrophic keratopathy are ongoing - these exciting clinical possibilities for TB-500 in the eye result from seminal fundamental scientific discoveries. Researchers believe Thymosin Beta-4 eyedrops will help many patients suffering from several ocular disorders, including dry eye.

TB-500 is a Potential Regulator of Hepatic Stellate Cells

Liver fibrosis, a significant characteristic of chronic liver disease, is inappropriate tissue remodeling induced by prolonged parenchymal cell inflammation and injury. During liver injury, hepatic stellate cells (HSCs) undergo transdifferentiation from quiescent HSCs into activated HSCs, which encourage the deposition of extracellular matrix proteins, leading to liver fibrosis.

Thymosin Beta-4, a major actin-sequestering protein, controls cell morphogenesis and motility by regulating the dynamics of the actin cytoskeleton. Thymosin Beta-4 is also known to be involved in various cellular responses, including angiogenesis, anti inflammation, wound healing, and cancer progression. 

Emerging evidence suggests that TB-500 is expressed in the liver; recent findings show different effects regarding the function of this peptide in various tissues and the potential role in liver fibrosis, with a special focus on the effects of endogenous and exogenous Thymosin Beta-4. 

Recent studies have revealed that activated HSCs express Thymosin Beta-4 in vivo and in vitro. Treatment with the exogenous peptide inhibits the migration and proliferation of activated HSCs and reduces liver fibrosis, indicating it has an anti-fibrotic action. Meanwhile, the endogenously expressed peptide in activated HSCs is shown to promote HSC activation.

Summary

In conclusion, scientific research on peptides will continue to expand our understanding and knowledge of their potential benefits. These discoveries open exciting possibilities for future medical applications. 

Please note that TB-500 peptide is currently being used for research purposes only and is not approved for human use. As science develops every day, exploring peptides may pave the way for new therapeutic solutions.

New research shows that TB-500 has so much potential, and it will definitely be studied more in the future.

References:

1. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008 May 15;453(7193):314-21. doi: 10.1038/nature07039. PMID: 18480812.
2. Huff, T., Müller, C. S., Otto, A. M., Netzker, R., & Hannappel, E. (2001). beta-Thymosins, small acidic peptides with multiple functions. The international journal of biochemistry & cell biology, 33(3), 205–220. https://doi.org/10.1016/s1357-2725(00)00087-x
3. Freeman, K. W., Bowman, B. R., & Zetter, B. R. (2011). Regenerative protein thymosin beta-4 is a novel regulator of purinergic signaling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 25(3), 907–915. https://doi.org/10.1096/fj.10-169417
4. Dubé, K. N., & Smart, N. (2018). Thymosin β4 and the vasculature: multiple roles in development, repair and protection against disease. Expert opinion on biological therapy, 18(sup1), 131–139. doi:10.1080/14712598.2018.1459558
5. Philp, D., Goldstein, A. L., & Kleinman, H. K. (2004). Thymosin beta4 promotes angiogenesis, wound healing, and hair follicle development. Mechanisms of ageing and development, 125(2), 113–115. doi:10.1016/j.mad.2003.11.005
6. Santra, M., Zhang, Z. G., Yang, J., Santra, S., Santra, S., Chopp, M., & Morris, D. C. (2014). Thymosin β4 up-regulation of microRNA-146a promotes oligodendrocyte differentiation and suppression of the Toll-like proinflammatory pathway. The Journal of biological chemistry, 289(28), 19508–19518. https://doi.org/10.1074/jbc.M113.529966
7. Sosne, G., Qiu, P., & Kurpakus-Wheater, M. (2007). Thymosin beta 4: A novel corneal wound healing and anti-inflammatory agent. Clinical ophthalmology (Auckland, N.Z.), 1(3), 201–207.
8. Srivastava, D., Ieda, M., Fu, J., & Qian, L. (2012). Cardiac repair with thymosin β4 and cardiac reprogramming factors. Annals of the New York Academy of Sciences, 1270, 66–72. https://doi.org/10.1111/j.1749-6632.2012.06696.x
9. Bock-Marquette, I., Saxena, A., White, M. D., Dimaio, J. M., & Srivastava, D. (2004). Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature, 432(7016), 466–472. target=”_blank” rel=”noopener”https://doi.org/10.1038/nature03000