Thymosin Beta-4 Induces Mouse Hair Growth

PLoS One. 2015 Jun 17;10(6):e0130040. doi: 10.1371/journal.pone.0130040. eCollection 2015.

Abstract

Thymosin beta-4 (Tβ4) is known to induce hair growth and hair follicle (HF) development; however, its mechanism of action is unknown. We generated mice that overexpressed Tβ4 in the epidermis, as well as Tβ4 global knockout mice, to study the role of Tβ4 in HF development and explore the mechanism of Tβ4 on hair growth. To study Tβ4 function, we depilated control and experimental mice and made tissue sections stained with hematoxylin and eosin (H&E). To explore the effect of Tβ4 on hair growth and HF development, the mRNA and protein levels of Tβ4 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 Tβ4-overexpressing mice, but slower in knockout mice. Histological examination revealed that Tβ4-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 Tβ4 expression at the mRNA and protein levels was confirmed in Tβ4-overexpressing mice, which also had increased VEGF expression. On the other hand, knockout mice had reduced levels of VEGF expression. Mechanistically, Tβ4-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. Tβ4 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Epidermis / metabolism
  • Gene Expression Regulation
  • Gene Knockout Techniques
  • Hair / cytology
  • Hair / growth & development*
  • Hair / physiology
  • Hair Follicle / blood supply
  • Hair Follicle / cytology
  • Hair Follicle / growth & development
  • Humans
  • MAP Kinase Signaling System
  • Mice
  • Neovascularization, Physiologic
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinase C / metabolism
  • Thymosin / deficiency
  • Thymosin / genetics
  • Thymosin / metabolism*
  • Vascular Endothelial Growth Factor A / genetics
  • Wnt Signaling Pathway

Substances

  • Vascular Endothelial Growth Factor A
  • thymosin beta(4)
  • Thymosin
  • Phosphatidylinositol 3-Kinases
  • Protein Kinase C

Grants and funding

This work was supported by the Program of National Natural Science Foundation of China (Grant No. 31160228) and The National High Technology Research and Development Program of China (863 Program)(Grant No. 2013AA102506). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.