Thymosin Beta-4 Induces Mouse Hair Growth

Thymosin beta-4 (T beta 4) is known to induce hair growth and hair follicle (HF) development; however, its mechanism of action is unknown. We generated mice that overexpressed T beta 4 in the epidermis, as well as T beta 4 global knockout mice, to study the role of T beta 4 in HF development and explore the mechanism of T beta 4 on hair growth. To study T beta 4 function, we depilated control and experimental mice and made tissue sections stained with hematoxylin and eosin (H&E). To explore the effect of T beta 4 on hair growth and HF development, the mRNA and protein levels of T beta 4 and VEGF were detected by real-time PCR and western blotting in control and experimental mice. Protein expression levels and the phosphorylation of P38, ERK and AKT were also examined by western blotting. The results of depilation indicated that hair re-growth was faster in T beta 4-overexpressing mice, but slower in knockout mice. Histological examination revealed that T beta 4-overexpressing mice had a higher number of hair shafts and HFs clustered together to form groups, while the HFs of control mice and knockout mice were separate. Hair shafts in knockout mice were significantly reduced in number compared with control mice. Increased T beta 4 expression at the mRNA and protein levels was confirmed in T beta 4-overexpressing mice, which also had increased VEGF expression. On the other hand, knockout mice had reduced levels of VEGF expression. Mechanistically, T beta 4-overexpressing mice showed increased protein expression levels and phosphorylation of P38, ERK and AKT, whereas knockout mice had decreased levels of both expression and phosphorylation of these proteins. T beta 4 appears to regulate P38/ERK/AKT signaling via its effect on VEGF expression, with a resultant effect on the speed of hair growth, the pattern of HFs and the number of hair shafts.