What is TB 500?

2017-04-27

Thymosin

Thymosin is a hormone secreted from the thymus. This is the reason why it is named Thymosin. But most are now known to be present in many other tissues. Its primary function is to stimulate the production of T cells, which are an important part of the immune system. Thymosin also assists in the development of B cells to plasma cells to produce antibodies. It is classified as α, β and γ thymosins on the basis of their behaviour in an electric field. It is found that there are as many as 16 members of thymosin family, among which thymosin β4 (Tβ4), Tβ10 and Tβ15 are found in humans. Tβ4 is a 5.0 kDa member of β-thymosin molecular family. Thymosin has biological activities, and two in particular, thymosin α1 and thymosin β4, have potentially important uses in medicine, some of which have already progress from the laboratory to the clinic.

What is thymosin beta 4?

Thymosin β4 is also called TB-500, which is a lymphopoiesis promoting factor first extracted from calf thymus in 1966 by Goldstein et al. It is a peptide with 43 amino acids widely existing in human body. Natural Tβ4 is composed of 43 amino acids, and its amino acid sequence and secondary structure are shown in the following figure. Tβ4 lacks hydrophobic amino acids in its structure and belongs to water-soluble protein.

What is TB-500?

TB-500 is one of the main actin regulatory factors in human body, which has a wide range of biological activities and is closely related to cytoskeleton balance, inflammatory reaction, wound healing, vascular regeneration, cell apoptosis, corneal and myocardial repair. Many research results show that TB-500 is closely related to many physiological processes and has a very broad application prospect. It can be used to treat many diseases such as myocardialinfarction (MI), dry eye, corneal injury, compression ulcer, oral mucosal inflammation and lung injury.

Molecular structure and binding affinities of TB-500

TB-500 belongs to the beta-thymosin family of proteins, characterized by a conserved actin-binding motif. This motif enables TB-500 to bind to G-actin (globular actin), preventing its polymerization into F-actin (filamentous actin). This interaction is critical for maintaining the dynamic equilibrium of the cytoskeleton, which is essential for various cellular functions, including motility, division, and intracellular transport. The N-terminal region of TB-500 is particularly important for its actin-binding activity, while the C-terminal region contributes to its stability and solubility in the cellular environment.

Recent studies have also suggested that TB-500 may interact with other cellular proteins, expanding its functional repertoire. For instance, TB-500 has been implicated in the modulation of intracellular signaling pathways through its interactions with proteins such as PINCH (particularly interesting new cysteine-histidine rich protein) and ILK (integrin-linked kinase), which are involved in cell adhesion and signaling. These interactions further underscore the multifaceted roles of TB-500 in cellular biology.

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What is TB-500 used for?

Role in cellular migration and angiogenesis

One of the most significant functions of TB-500 is its ability to promote cellular migration, a process vital for tissue regeneration and repair. TB-500 facilitates cell motility by modulating the actin cytoskeleton and influencing the expression of genes involved in migration. Additionally, TB-500 has been shown to upregulate the expression of matrix metalloproteinases (MMPs), which degrade extracellular matrix components, thereby enabling cells to navigate through tissue barriers.

Angiogenesis, the formation of new blood vessels from existing vasculature, is another crucial process influenced by TB-500. This peptide stimulates the proliferation and migration of endothelial cells, which are the building blocks of new blood vessels. TB-500 achieves this by activating signaling pathways such as the phosphoinositide 3-kinase (PI3K)/Akt pathway and the extracellular signal-regulated kinase (ERK) pathway, both of which are integral to cell survival and proliferation. Moreover, TB-500 enhances the secretion of angiogenic factors like vascular endothelial growth factor (VEGF), further promoting vascular growth and repair.

Recent research has also indicated that TB-500 may have a role in the stabilization of newly formed blood vessels. It appears to support the maturation of these vessels by promoting the recruitment of pericytes and smooth muscle cells, which are essential for the structural integrity and functionality of mature blood vessels. This aspect of TB-500's activity is particularly relevant in pathological conditions characterized by aberrant angiogenesis, such as cancer and chronic inflammatory diseases.

Involvement in wound healing and tissue regeneration

TB-500's role in wound healing has garnered significant attention due to its ability to accelerate the repair of damaged tissues. It achieves this through multiple mechanisms, including the promotion of keratinocyte and fibroblast migration, which are essential for re-epithelialization and extracellular matrix formation, respectively. Additionally, TB-500 reduces inflammation by modulating the activity of inflammatory cells and cytokines, thereby creating a conducive environment for healing.

In animal models, TB-500 has been shown to enhance the healing of various types of wounds, including dermal, corneal, and myocardial injuries. For instance, in myocardial infarction models, TB-500 treatment resulted in reduced scar formation and improved cardiac function, likely due to its ability to stimulate cardiomyocyte survival and angiogenesis. These findings suggest that TB-500 could be a valuable therapeutic agent for promoting tissue regeneration in a range of medical conditions.

Moreover, TB-500 has been found to influence the expression of genes involved in tissue remodeling and repair. For example, it upregulates the expression of laminin-5, a key component of the basement membrane, which is crucial for cell adhesion and migration during wound healing. TB-500 also enhances the production of collagen, a major structural protein in the extracellular matrix, further supporting tissue repair and regeneration.

Anti-inflammatory properties

Inflammation is a double-edged sword, essential for initiating the healing process but potentially detrimental if uncontrolled. TB-500 plays a critical role in modulating inflammation, ensuring that it is beneficial rather than harmful. It exerts its anti-inflammatory effects by reducing the expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), while increasing the levels of anti-inflammatory cytokines like interleukin-10 (IL-10).

Furthermore, TB-500 inhibits the activation of nuclear factor-kappa B (NF-κB), a key transcription factor involved in the inflammatory response. By preventing NF-κB translocation to the nucleus, TB-500 reduces the expression of genes associated with inflammation and immune responses. This anti-inflammatory action is particularly relevant in chronic inflammatory conditions, where prolonged inflammation can lead to tissue damage and fibrosis.

In addition to its direct anti-inflammatory effects, TB-500 has been shown to modulate the activity of regulatory T cells (Tregs), which play a crucial role in maintaining immune homeostasis and preventing excessive inflammatory responses. By enhancing the function of Tregs, TB-500 contributes to the resolution of inflammation and the restoration of tissue integrity.

Neuroprotective effects

TB-500 also possesses neuroprotective properties, making it a potential candidate for the treatment of neurodegenerative diseases. TB-500 promotes neuronal survival and differentiation, possibly through its interaction with actin and the subsequent stabilization of the cytoskeleton. Additionally, TB-500 enhances the outgrowth of neurites, which are essential for the formation of neural networks and synaptic connections.

In models of central nervous system (CNS) injury, such as spinal cord injury and traumatic brain injury, TB-500 administration has been associated with reduced neuronal loss, improved functional recovery, and enhanced regeneration of neural tissues. These findings indicate that TB-500 could play a significant role in neuroregeneration and the treatment of CNS disorders.

Furthermore, TB-500 has been shown to reduce oxidative stress and apoptosis in neuronal cells, which are common features of neurodegenerative diseases. By enhancing the expression of antioxidant enzymes and inhibiting the activation of pro-apoptotic pathways, TB-500 helps to preserve neuronal viability and function. These neuroprotective effects make TB-500 a promising candidate for further research in the field of neurology.

Potential in stem cell research

The regenerative capabilities of TB-500 extend to its potential applications in stem cell research. TB-500 has been shown to promote the proliferation and differentiation of various stem cell types, including mesenchymal stem cells (MSCs) and neural stem cells (NSCs). By influencing the stem cell microenvironment, TB-500 enhances their regenerative potential and facilitates the repair of damaged tissues.

Moreover, TB-500 can enhance the homing and engraftment of stem cells to injury sites, a critical factor for effective stem cell therapy. This is particularly important for the treatment of ischemic injuries, where timely and targeted delivery of stem cells can significantly improve outcomes. The combination of TB-500 with stem cell therapy could, therefore, represent a powerful approach for tissue regeneration and repair.

In addition to promoting stem cell proliferation and differentiation, TB-500 has been shown to enhance the survival and functionality of transplanted stem cells. By creating a supportive microenvironment and reducing inflammatory responses, TB-500 helps to ensure that transplanted stem cells can effectively integrate into host tissues and contribute to the repair process. This synergistic effect of TB-500 and stem cells holds great promise for the development of advanced regenerative therapies.

TB-500 is a multifunctional peptide with a wide range of biological activities that are crucial for cellular function, tissue repair, and regeneration. Its ability to modulate the actin cytoskeleton, promote angiogenesis, accelerate wound healing, and exert anti-inflammatory and neuroprotective effects highlights its therapeutic potential. While the clinical applications of TB-500 are still under investigation, its profound impact on fundamental biological processes makes it a promising candidate for further research and development in the field of regenerative medicine.

References

  1. Lee, J. Y.; et al. Synthesis and biological screening of small molecule peptides based on the amino acid sequence of thymosin β4. Journal of the Korean Society for Applied Biological Chemistry. 2015, 58: 651-658.
  2. Nie, L.; et al. Thymosin β4 impeded murine stem cell proliferation with an intact cardiovascular differentiation. Journal of Huazhong University of Science and Technology. 2016, 36: 328-334.

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