Thymosin beta 4 (Thymosin β4)

Thymosin β4 is a major actin sequestering protein in cells and can interact with G-actin^[1,2]. Thymosin β4 is found in many vertebrate tissues and cells and is especially concentrated in macrophages, fibroblasts, neutrophils, and platelets, which have large pools of G-actin^[3]. The main physiological role of Thymosin β4 is the regulation of actin polymerization. Thymosin β4 is also involved in angiogenesis, cell survival, cell migration and fetal development^[4].

Thymosin β4 plays a crucial role in the regulation of tight junction stability and acts in cytoskeleton rearrangement, which are closely related with BBB permeability^[2]. Thymosin β4 is a novel regulator for primary cilia formation and it affects ciliogenesis by regulating the expression of NPHP3 in HeLa cervical cancer cells^[5]. Thymosin β4 regulates HSC activation by influencing the activity of Smoothened and GLI2, suggesting Thymosin β4 as a novel therapeutic target in liver disease^[6]. Synthetic Thymosin β4 peptide increases NK cell cytotoxicity mediated by intercellular adhesion molecule^-1 (ICAM^-1 ) through the secretion of cytolytic granules to target cells, suggests that Thymosin β4 is a key activator of NK cell cytotoxicity^[7].

Thymosin β4 enhanced wound healing in a rat full thickness wound model suggest that Thymosin β4 is a potent wound healing factor with multiple activities^[1]. Thymosin β4 administration during gestation may act as a powerful fetal growth promoter, by accelerating the development of newborn organs and tissues^[4].Recombinant Human Thymosin β4 significantly increased the survival rate of mice infected with MHV-A59 through inhibiting virus replication, balancing the host’s immune response, alleviating pathological damage, and promoting repair of the liver^[8].

References:
[1]. Malinda KM, Sidhu GS, et al. Thymosin beta4 accelerates wound healing. J Invest Dermatol. 1999;113(3):364-368.
[2]. Song K, Han HJ, et al. Thymosin beta 4 attenuates PrP(106-126)-induced human brain endothelial cells dysfunction. Eur J Pharmacol. 2020;869:172891.
[3]. Weber A, Nachmias VT, et al, Safer D. Interaction of thymosin beta 4 with muscle and platelet actin: implications for actin sequestration in resting platelets. Biochemistry. 1992;31(27):6179-6185.
[4]. Faa G, Piras M, et al. Thymosin beta-4 prenatal administration improves fetal development and halts side effects due to preterm delivery. Eur Rev Med Pharmacol Sci. 2021;25(1):431-437.
[5]. Lee JW, Kim HS, et al. Thymosin β-4 is a novel regulator for primary cilium formation by nephronophthisis 3 in HeLa human cervical cancer cells. Sci Rep. 2019;9(1):6849. Published 2019 May 2.
[6]. Kim J, Hyun J, et al. Thymosin beta-4 regulates activation of hepatic stellate cells via hedgehog signaling. Sci Rep. 2017;7(1):3815. Published 2017 Jun 19.
[7]. Lee HR, Yoon SY, et al. Thymosin beta 4 enhances NK cell cytotoxicity mediated by ICAM-1. Immunol Lett. 2009;123(1):72-76.
[8]. Yu R, Mao Y, et al. Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection. Mediators Inflamm. 2021;2021:9979032. Published 2021 Apr 21.