A Cell-Based System for Screening Hair Growth-Promoting Agents

Arch Dermatol Res. 2009 Jun;301(5):381-5. doi: 10.1007/s00403-009-0931-0. Epub 2009 Mar 11.

Abstract

Androgen-inducible transforming growth factor beta (TGF-beta1) derived from dermal papilla cells (DPCs) is a catagen inducer that mediates hair growth suppression in androgenetic alopecia (AGA). In this study, a cell-based assay system was developed to monitor TGF-beta1 promoter activity and then used to evaluate the effects of activated TGF-beta1 promoter in human epidermal keratinocytes (HaCaT). To accomplish this, a pMetLuc-TGF-beta1 promoter plasmid that expresses the luciferase reporter gene in response to TGF-beta1 promoter activity was constructed. Treatment of HaCaT with dihydrotestosterone, which is known to be a primary factor of AGA, resulted in a concentration-dependent increase in TGF-beta1 promoter activity. However, treatment of HaCaT with the TGF-beta1 inhibitor, curcumin, resulted in a concentration-dependant decrease in TGF-beta1 expression. Subsequent use of this assay system to screen TGF-beta1 revealed that HaCaT that were treated with apigenin showed decreased levels of TGF-beta1 expression. In addition, treatment with apigenin also significantly increased the proliferation of both SV40T-DPCs (human DPCs) and HaCaT cells. Furthermore, apigenin stimulated the elongation of hair follicles in a rat vibrissa hair follicle organ culture. Taken together, these findings suggest that apigenin, which is known to have antioxidant, anti-inflammatory, and anti-tumor properties, stimulates hair growth through downregulation of the TGF-beta1 gene. In addition, these results suggest that this assay system could be used to quantitatively measure TGF-beta1 promoter activity in HaCaT, thereby facilitating the screening of agents promoting hair growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alopecia / immunology*
  • Alopecia / pathology
  • Alopecia / physiopathology
  • Alopecia / therapy
  • Animals
  • Apigenin / pharmacology
  • Cell Culture Techniques
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / immunology
  • Curcumin / pharmacology
  • Drug Evaluation, Preclinical / methods*
  • Epidermis / pathology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Hair / drug effects
  • Hair / growth & development
  • Hair / immunology
  • Hair / metabolism*
  • Humans
  • Immunotherapy*
  • Keratinocytes / drug effects
  • Keratinocytes / immunology
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Promoter Regions, Genetic
  • Rats
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / immunology
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / immunology
  • Transforming Growth Factor beta1 / metabolism*
  • Vibrissae / drug effects
  • Vibrissae / immunology
  • Vibrissae / metabolism*
  • Vibrissae / pathology

Substances

  • Transforming Growth Factor beta1
  • Apigenin
  • Curcumin