The effects of Tβ4 over- (KTP) and under- (KO) expression on hair follicle regeneration (represented as hair shaft growth) in mice with corresponding Tβ4 and VEGF expression levels. From Gao X, Liang H, Hou F, et al. Thymosin Beta-4 Induces Mouse Hair Growth. PloS one. 2015;10(6):e0130040, reproduced under the terms of the Creative Commons Attribution License

The effects of Tβ4 over- (KTP) and under- (KO) expression on hair follicle regeneration (represented as hair shaft growth) in mice with corresponding Tβ4 and VEGF expression levels. From Gao X, Liang H, Hou F, et al. Thymosin Beta-4 Induces Mouse Hair Growth. PloS one. 2015;10(6):e0130040, reproduced under the terms of the Creative Commons Attribution License

Thymosin beta4 (Tβ4) is a peptide made of 43 amino acids. It is, as the name suggests, found in the thymus gland of a number of animals1. Tβ4 plays a role in the process of cellular movement (or migration) by recruiting actin2. It may regulate this by preventing the formation of actin complexes by binding the individual units of this protein2. Tβ4 has the potential to orchestrate cellular differentiation and co-ordination (which is required for events such as neovascularization) through this form of control over the local populations of actin. It is mostly found within cells, but extracellular Tβ4 may be detected in plasma and in injured tissues2. The peptide may have a role in recovery from tissue damage.  Tβ4 and Neural Cells Tβ4 has been observed to promote the development of nerve cells. It may be associated with the increased differentiation of progenitor-type cells into oligodendrocytes, a long, thin variety of neural cells3. Tβ4 may also have a protective effect in rat models of acquired brain injury3. The peptide stimulates increased levels of microRNA 200a (miR200a) in brain cells. miR200a has a negative effect on epidermal growth factor receptor-associated signaling, which activates p533. As p53 would induce apoptosis in brain cells exposed to oxygen deprivation, Tβ4 ultimately promotes the preservation of nerve cells and their precursors following adverse events such as hypoxia. Another study using murine oligodendrocyte-precursor cell lines found that Tβ4 also upregulated microRNA 146a (miR146a), which in turned down-regulated an inflammatory response mediated by the Toll-like receptor. Tβ4 administration also resulted in reductions in the levels of tumor necrosis factor receptor-associated factor 6 (TRAF6) and IL-1 receptor-associated kinase 1 (IRAK1), which also promote inflammation4. Inflammation is related to further cellular damage and death following an injury or other similar event in environments such as oligodendrocyte-rich nervous tissue. Therefore, treatment with Tβ4 may help conserve cell health and numbers after this damage. Tβ4 in Other Tissues  Tβ4 may promote tissue healing and remodeling in additional cell types. A study investigated the effects of the peptide in a mouse model of myocardial infarction (an event associated with markedly increased inflammation and tissue damage that may be fatal5). Tβ4 administration for seven days after experimental infarction resulted in decreased infiltrations into cardiac tissue by inflammatory cells, as well as reduced cardiac muscle cell death, compared to animals treated with an identical sham treatment5. The animals receiving Tβ4 also exhibited a significant restoration of cardiac function, reduced cardiac scarring and decreased death rates after five weeks compared to control animals5. Tβ4 may also be associated with positive effects on the functions of hair follicles. This was investigated in a study using mice overexpressing Tβ4, mice with non-functional Tβ4 genes (or Tβ4-knockout) and normal mice as controls. The researchers removed hair from groups of all of these mouse types. They found that the number of new hair shafts in Tβ4-knockout were significantly reduced compared to control mice, and that their follicles did not form clusters as normal6. The mice who over-expressed Tβ4 exhibited new hair growth that was faster and thicker than that of controls6. These effects appeared to be mediated via MAPK signaling, and were also correlated with the expression of VEGF in the skin6. References: 1. Goldstein AL, Slater FD, White A. Preparation, assay, and partial purification of a thymic lymphocytopoietic factor (thymosin). Proceedings of the National Academy of Sciences of the United States of America. 1966;56(3):1010-1017. 2. Huff T, Muller CS, Otto AM, Netzker R, Hannappel E. beta-Thymosins, small acidic peptides with multiple functions. The international journal of biochemistry & cell biology. 2001;33(3):205-220. 3. Santra M, Chopp M, Santra S, et al. Thymosin beta 4 up-regulates miR-200a expression and induces differentiation and survival of rat brain progenitor cells. Journal of neurochemistry. 2015. 4. Santra M, Zhang ZG, Yang J, et al. Thymosin beta4 up-regulation of microRNA-146a promotes oligodendrocyte differentiation and suppression of the Toll-like proinflammatory pathway. The Journal of biological chemistry. 2014;289(28):19508-19518. 5. Peng H, Xu J, Yang XP, et al. Thymosin-beta4 prevents cardiac rupture and improves cardiac function in mice with myocardial infarction. American journal of physiology. Heart and circulatory physiology. 2014;307(5):H741-751. 6. Gao X, Liang H, Hou F, et al. Thymosin Beta-4 Induces Mouse Hair Growth. PloS one. 2015;10(6):e0130040.