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.

胸腺素 β4 是细胞中主要的肌动蛋白螯合蛋白，可与 G-肌动蛋白相互作用^[1,2]。胸腺素 β4 存在于许多脊椎动物组织和细胞中，尤其集中在巨噬细胞、成纤维细胞、中性粒细胞和血小板中，这些细胞具有大量 G-肌动蛋白^[3]。胸腺素 β4 的主要生理作用是调节肌动蛋白聚合。胸腺肽 β4 还参与血管生成、细胞存活、细胞迁移和胎儿发育^[4]。

胸腺素β4在调节紧密连接稳定性和细胞骨架重排中起着至关重要的作用，与血脑屏障通透性密切相关^[2]。 Thymosin β4 是一种新的初级纤毛形成调节因子，它通过调节宫颈癌细胞 NPHP3 的表达影响纤毛生成^[5]。 Thymosin β4 通过影响 Smoothened 和 GLI2 的活性来调节 HSC 活化，表明 Thymosin β4 可作为肝病治疗的新靶点^[6]。合成的 Thymosin β4 肽通过向靶细胞分泌细胞溶解颗粒增加由细胞间粘附分子^-1 (ICAM^-1 ) 介导的 NK 细胞细胞毒性，表明 Thymosin β4 是一种NK细胞细胞毒性的关键激活剂^[7].

Thymosin β4 在大鼠全层伤口模型中促进伤口愈合表明 Thymosin β4 是一种具有多种活性的有效伤口愈合因子^[1]。妊娠期间给予胸腺素 β4 可作为强大的胎儿生长促进剂，通过加速新生儿器官和组织的发育^[4]。重组人胸腺素 β4 显着提高了感染 MHV-A59 的小鼠的存活率通过抑制病毒复制，平衡宿主免疫反应，减轻病理损伤，促进肝脏修复^[8]。