Research Advances in ABP-7 Peptide and Tissue Repair

ABP-7 (actin binding peptide-7) is a heptapeptide consisting of the amino acid sequence Acetyl-LKKTETQ⁽¹⁾. Identified as an N-acylated fragment of the larger molecule Thymosin Beta 4, ABP-7 is also referred to as the TB-500 Fragment.

Research suggests that this synthetic peptide is produced through solid-phase peptide synthesis,⁽²⁾ highlighting its designed nature for targeted scientific exploration. The sequence LKKTETQ within ABP-7 is hypothesized to represent the primary actin-binding domain of Thymosin Beta 4, suggesting that ABP-7 might mimic some of the functional properties of its parent molecule.

Fig. 1. Thymosin Beta 4

Thymosin Beta 4, a known actin-binding protein, is speculated to exert its function primarily through the domain that includes ABP-7. This domain is notable for inhibiting the polymerization of globular actin (G-actin) into filamentous actin (F-actin), deemed a critical process for maintaining cellular structure and function. By sequestering G-actin, ABP-7 might potentially maintain higher intracellular levels of actin in its monomeric form, thereby impacting cellular motility and shape adaptation.

Scientific studies suggest that actin plays a crucial role in the cytoskeleton, providing structural support and facilitating various cellular activities such as motility and morphological changes. The reported stabilization of G-actin by ABP-7, which prevents its polymerization into F-actin, may disrupt the cytoskeletal architecture, influencing essential cellular processes including migration, wound healing, and tissue regeneration. These potential effects on actin dynamics suggest that ABP-7 might be significant in modulating cellular behaviors, presenting opportunities for further exploration in various biological contexts.

 

Research

ABP-7 Peptide and Fibrotic Tissue Remodeling

Research has been conducted to explore the potential anti-fibrotic characteristics of ABP-7 peptide, focusing on its action on hepatic stellate cells (HSCs) in the context of liver fibrosis. Preliminary studies⁽³⁾ suggest that ABP-7 peptide “inhibits PDGF-BB-induced fibrogenesis, proliferation and migration of HSC by blocking Akt phosphorylation.” Additionally, ABP-7 appears to obstruct the phosphorylation of Akt at the T308 and S473 sites, which may subsequently impede the phosphorylation of PRAS40.

The PDGF-BB-dependent upregulation is believed to involve an enhancement of cellular signals initiated by PDGF-BB, a platelet-derived growth factor that activates the PDGFβ receptor. Researchers noted that ABP-7 might prevent the PDGF-BB-induced reappearance of the receptor protein after its degradation. This receptor is considered crucial for cellular growth and division.

α-Smooth muscle actin (α-SMA) serves as a marker for the transition of quiescent stellate cells into their contractile phenotype, a critical event in fibrosis development. Collagen type I is considered a principal component of the extracellular matrix that accumulates during liver fibrosis. The phosphorylation of Akt at T308 and S473 sites is hypothesized to activate Akt, leading to the activation of several downstream proteins, including PRAS40, an essential regulator of cell survival and metabolism. Inhibition of these phosphorylation events may disrupt these signaling pathways, vital for cell proliferation and migration in fibrogenesis.

The potential inhibition of these pathways by ABP-7 may correlate with a reduction in the proliferation and migration of activated HSCs. These observations suggest that ABP-7 might play an influential role in mitigating the activation of HSCs and the subsequent fibrotic response.

ABP-7 Peptide and Dermal Regeneration

A study⁽⁴⁾ was conducted to assess the action of ABP-7, recognized as the central actin-binding domain of Thymosin Beta 4 (Tb4), on wound repair in aged murine models. The potential of this peptide to augment wound healing was evaluated by analyzing parameters such as keratinocyte migration, collagen deposition, and wound closure. Researchers hypothesized that “the actin-binding domain of Thymosin Beta 4 duplicated in a seven-amino acid synthetic peptide, LKKTETQ, was able to promote repair in aged animals comparable to that observed with the parent molecule.” The findings indicate that ABP-7 may facilitate wound repair in aged murine models similarly to Tb4.

ABP-7 is proposed to stimulate epidermal cell migration and augment collagen deposition at the wound site, potentially expediting wound closure and healing. Thymosin Beta 4 and its derivatives, including ABP-7, have been investigated for their potential to enhance keratinocyte migration, an aspect of the healing process. By mimicking a specific functional domain of Tb4, ABP-7 likely engages similar biological pathways to promote wound repair. However, further research is necessary to comprehensively elucidate the peptide’s mechanism of action and its implications in wound healing.

Various studies have proposed mechanisms through which ABP-7 may accelerate the healing of lesions and skin wounds. One proposed mechanism involves the interaction of ABP-7 with purinergic receptors, which appear to play pivotal roles in cellular responses to injury. This interaction may elevate intracellular calcium levels, factors in activating pathways conducive to wound closure. Increased calcium levels may stimulate processes such as cell migration and extracellular matrix remodeling, deemed vital for wound repair.

Furthermore, ABP-7’s interaction with actin, a fundamental component of the cellular cytoskeleton, suggests a mechanism by which ABP-7 may modulate actin dynamics. By binding to actin, ABP-7 might potentially stabilize or alter the cytoskeletal structure, thereby enhancing cell migration and wound coverage. Moreover, ABP-7 may activate downstream signaling pathways, such as those mediated by MAP kinases, which appear to govern gene expression associated with cell proliferation and migration. The modulation of these pathways by ABP-7 might augment cellular responses essential for wound healing.

ABP-7 Peptide and Angiogenesis

The ABP-7 peptide appears to play a potential role in promoting angiogenesis, the process of new blood vessel formation. It is hypothesized that ABP-7 may facilitate endothelial cell behaviors necessary for angiogenesis, including migration and tube formation in vitro. These processes are integral to angiogenesis, wherein endothelial cells migrate, align, and form tubular structures to establish new vascular networks. Ex vivo assays, such as sprouting from aortic rings, have suggested that ABP-7 may support the initial stages of vessel sprouting, a recognized step in angiogenesis.⁽⁵⁾

Researchers propose that ABP-7’s actin-binding activity may reduce the interaction of actin with other cellular components, potentially enabling actin to participate more actively in the dynamic structural changes that endothelial cells undergo during angiogenesis. By modifying actin availability or organization within endothelial cells, ABP-7 may influence cellular architecture in a manner conducive to angiogenic processes, including alterations in cell shape and motility critical for vascular structure formation. Considering the multifaceted nature of angiogenic signaling and the numerous steps involved, ABP-7 might also interact indirectly with other cellular pathways or signaling molecules contributing to angiogenesis.

The potential interactions of ABP-7 and its effects on angiogenesis remain subjects of ongoing investigation, offering avenues for further exploration in future studies.

ABP-7 Peptide and Hair Follicle Dynamics

The serendipitous revelation regarding ABP-7 peptide’s influence on hair growth stemmed from experimental observations involving laboratory mice. Initial reports suggest that the mice lacking genetic expression of Thymosin Beta-4 (TB-4) exhibited notably delayed hair regrowth following shaving compared to wild-type mice. Conversely, the microscopic examination of these mice revealed augmented hair shaft density and clustered hair follicles, indicative of possible enhanced hair regeneration process. As a result of this, researchers state that they have “determined the mechanism by which thymosin beta 4 acts to promote hair growth by examining its effects on follicle stem cell growth, migration, differentiation, and protease production.” ⁽⁶⁾

 
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References:

1. Ho EN, Kwok WH, Lau MY, Wong AS, Wan TS, Lam KK, Schiff PJ, Stewart BD. Doping control analysis of TB-500, a synthetic version of an active region of thymosin β₄, in equine urine and plasma by liquid chromatography-mass spectrometry. J Chromatogr A. 2012 Nov 23;1265:57-69. doi: 10.1016/j.chroma.2012.09.043. Epub 2012 Sep 23. https://pubmed.ncbi.nlm.nih.gov/23084823/
2. Esposito, S., Deventer, K., Goeman, J., Van der Eycken, J., & Van Eenoo, P. (2012). Synthesis and characterization of the N-terminal acetylated 17-23 fragment of thymosin beta 4 identified in TB-500, a product suspected to possess doping potential. Drug testing and analysis, 4(9), 733–738. https://doi.org/10.1002/dta.1402
3. Shah, R., Reyes-Gordillo, K., & Rojkind, M. (2018). Thymosin β4 inhibits PDGF-BB induced activation, proliferation, and migration of human hepatic stellate cells via its actin-binding domain. Expert opinion on biological therapy, 18(sup1), 177–184. https://doi.org/10.1080/14712598.2018.1478961
4. Philp, D., Badamchian, M., Scheremeta, B., Nguyen, M., Goldstein, A. L., & Kleinman, H. K. (2003). Thymosin beta 4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 11(1), 19–24. https://doi.org/10.1046/j.1524-475x.2003.11105.x
5. Sosne, G., Qiu, P., Goldstein, A. L., & Wheater, M. (2010). Biological activities of thymosin beta4 defined by active sites in short peptide sequences. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 24(7), 2144–2151. https://doi.org/10.1096/fj.09-142307
6. Philp D, St-Surin S, Cha HJ, Moon HS, Kleinman HK, Elkin M. Thymosin beta 4 induces hair growth via stem cell migration and differentiation. Ann N Y Acad Sci. 2007 Sep;1112:95-103. doi: 10.1196/annals.1415.009. PMID: 17947589. https://pubmed.ncbi.nlm.nih.gov/17947589/
7. Image Source: National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 16132341, Thymosin beta4. https://pubchem.ncbi.nlm.nih.gov/compound/Thymosin-beta4.