Thymosin β-4 (Tβ
4), a ubiquitous, abundant intracellular peptide consisting of 43 amino acids, regulates the actin monomer pool by sequestering G-actin.
16 17 It has pleiotropic effects on different types of cells, such as increasing the rate of attachment and spread of endothelial cells on matrix components and stimulating the migration of human umbilical vein endothelial cells,
18 promoting cardiomyocyte migration and cardiac repair through activating integrin-linked kinase
19 20 and promoting matrix metalloproteinase expression during dermal wound repair.
21 Upregulation of Tβ
4 increases the invasive ability of human colorectal carcinoma cells by promoting the disruption of cell-cell adhesion and a consequential activation of β-catenin signaling,
22 23 and overexpression of Tβ
4 renders SW480 colon carcinoma cells more resistant to apoptosis triggered by FasL and two topoisomerase II inhibitors via downregulating Fas and upregulating survivin expression.
24 By contrast, the functions of exogenous Tβ
4 appear to be very different from those of the endogenous peptide. For example, this peptide has been reported to increase hair growth by stimulating the migration of hair follicle stem cells,
25 to induce plasminogen activator inhibitor (PAI)-1 secretion by endothelial cells, and to modulate the fibrinolytic potential of endothelial cells.
26 27 On the contrary, Tβ
4 and its N-terminal tetrapeptide, AcSDKP, have been shown to inhibit the proliferation of hematopoietic progenitor cells.
28 Anti-inflammatory effects of Tβ
4 and its sulfoxide adduct have also been demonstrated.
29 In corneal epithelial cells, wound healing promotion, inflammation reduction,
30 31 and inhibition of ethanol-induced
32 or benzalkonium chloride-triggered apoptosis
33 by exogenous Tβ
4 have been reported. However, the precise mechanism of the protective effect of this G-actin-sequestering peptide against various injuries in corneal epithelial cells is not fully understood.