A cell-based system for screening hair growth-promoting agents

  • Sungran Huh
  • Jongsung Lee
  • Eunsun Jung
  • Sang-Cheol Kim
  • Jung-Il Kang
  • Jienny Lee
  • Yong-Woo Kim
  • Young Kwan Sung
  • Hee-Kyoung Kang
  • Deokhoon Park
Short Communication

Abstract

Androgen-inducible transforming growth factor β (TGF-β1) 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-β1 promoter activity and then used to evaluate the effects of activated TGF-β1 promoter in human epidermal keratinocytes (HaCaT). To accomplish this, a pMetLuc-TGF-β1 promoter plasmid that expresses the luciferase reporter gene in response to TGF-β1 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-β1 promoter activity. However, treatment of HaCaT with the TGF-β1 inhibitor, curcumin, resulted in a concentration-dependant decrease in TGF-β1 expression. Subsequent use of this assay system to screen TGF-β1 revealed that HaCaT that were treated with apigenin showed decreased levels of TGF-β1 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-β1 gene. In addition, these results suggest that this assay system could be used to quantitatively measure TGF-β1 promoter activity in HaCaT, thereby facilitating the screening of agents promoting hair growth.

Keywords

TGF-β1 Hair growth Apigenin Dermal papilla cell Hair follicle 

References

  1. 1.
    Danilenko DM, Ring BD, Yanagihara D, Benson W, Wiemann B, Starnes CO, Pierce GF (1995) Keratinocyte growth factor is an important endogenous mediator of hair follicle growth, development, and differentiation. Am J Pathol 147:145–154PubMedGoogle Scholar
  2. 2.
    Foitzik K, Lindner G, Mueller-Roever S, Maurer M, Botchkareva N, Botchkarev V, Handjiski B, Metz M, Hibino T, Soma T, Dotto GP, Paus R (2000) Control of murine hair follicle regression (catagen) by TGF-β1 in vivo. FASEB J 14:752–760PubMedGoogle Scholar
  3. 3.
    Gordon KJ, Blobe GC (2008) Role of transforming growth factor-beta superfamily signaling pathways in human disease. Biochim Biophys Acta 1782(4):197–228PubMedGoogle Scholar
  4. 4.
    Hardy MH (1992) The secret life of the hair follicle. Trends Genet 8:55–61PubMedGoogle Scholar
  5. 5.
    Hogan BL (1996) Bone morphogenetic proteins in development. Curr Opin Genet Dev 6:432–438. doi:10.1016/S0959-437X(96)80064-5 PubMedCrossRefGoogle Scholar
  6. 6.
    Inui S, Fukuzato Y, Nakajima T, Yoshikawa K, Itami S (2002) Androgen-inducible TGF-β1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth. FASEB J 16:1967–1969PubMedGoogle Scholar
  7. 7.
    Inui S, Fukuzato Y, Nakajima T, Yoshikawa K, Itami S (2003) Identification of androgen-inducible TGF-β1 derived from dermal papilla cells as a key mediator in androgenetic alopecia. J Invest Dermatol Symp Proc 8:69–71. doi:10.1046/j.1523-1747.2003.12174.x CrossRefGoogle Scholar
  8. 8.
    Jahoda CA, Reynolds AJ (1996) Dermal-epidermal interactions. Adult follicle-derived cell populations and hair growth. Dermatol Clin 14:573–583. doi:10.1016/S0733-8635(05)70385-5 Google Scholar
  9. 9.
    Kim SJ, Angel P, Hattori K, Kim KY, Sporn MB, Karin M, Roberts AB (1990) Autoinduction of transforming growth factor beta 1 is mediated by the AP-1 complex. Mol Cell Biol 10:1492–1497PubMedGoogle Scholar
  10. 10.
    Kim SJ, Glick A, Sporn MB, Roberts AB (1989) Characterization of the promoter region of the human transforming growth factor-β1 gene. J Biol Chem 264:402–408PubMedGoogle Scholar
  11. 11.
    Kligman AM (1959) The human hair cycle. J Invest Dermatol 33:307–316PubMedGoogle Scholar
  12. 12.
    Lindner G, Botchkarev VA, Botchkareva NV, Ling G, van der Veen C, Paus R (1997) Analysis of apoptosis during hair follicle regression (catagen). Am J Pathol 151:1601–1617PubMedGoogle Scholar
  13. 13.
    Moses HL, Serra R (1996) Regulation of differentiation by TGF-β. Curr Opin Genet Dev 6:581–586. doi:10.1016/S0959-437X(96)80087-6 PubMedCrossRefGoogle Scholar
  14. 14.
    Park SY, Kwack MH, Chung EJ, Im SU, Kim MK, Kim JC, Sung YK (2007) Establishment of SV40T-transfected human dermal papilla cells and identification of dihydrotestosterone-regulated genes by cDNA microarray. J Dermatol Sci 47:201–208. doi:10.1016/j.jdermsci.2007.04.005 PubMedCrossRefGoogle Scholar
  15. 15.
    Paus R, Foitzik K, Bulfoned-Paus S, Eichmuller S (1997) Transforming growth factor-beta receptor type I and type II expression during murine hair follicle development and cycling. J Invest Dermatol 109:518–526. doi:10.1111/1523-1747.ep12336635 PubMedCrossRefGoogle Scholar
  16. 16.
    Paus R, Cotsarelis G (1999) The biology of hair follicles. N Engl J Med 341:491–497. doi:10.1056/NEJM199908123410706 PubMedCrossRefGoogle Scholar
  17. 17.
    Philpott MP, Sanders D, Westgate GE, Kealey T (1994) Human hair growth in vitro: a model for the study of hair follicle biology. J Dermatol Sci 7(Suppl):S55–S72. doi:10.1016/0923-1811(94)90036-1 PubMedCrossRefGoogle Scholar
  18. 18.
    Seiberg M, Marthinuss J, Stenn KS (1995) Changes in expression of apoptosis-associated genes in skin mark early catagen. J Invest Dermatol 104:78–82. doi:10.1111/1523-1747.ep12613555 PubMedCrossRefGoogle Scholar
  19. 19.
    Stenn KS, Combates NJ, Eilertsen KJ, Gordon JS, Pardinas JR, Parimoo S, Prouty SM (1996) Hair follicle growth controls. Dermatol Clin 14:543–558. doi:10.1016/S0733-8635(05)70383-1 PubMedCrossRefGoogle Scholar
  20. 20.
    Weigert C, Sauer U, Brodbeck K, Pfeiffer A, Haring HU, Schleicher ED (2000) AP-1 proteins mediate hyperglycemia-induced activation of the human TGF-β1 promoter in mesangial cells. J Am Soc Nephrol 11:2007–2016PubMedGoogle Scholar
  21. 21.
    Welker P, Foitzik K, Bulfone-Paus S, Henz BM, Paus R (1997) Hair cycle-dependent changes in the gene expression and protein content of transforming factor beta 1 and beta 3 in murine skin. Arch Dermatol Res 289:554–557. doi:10.1007/s004030050239 PubMedCrossRefGoogle Scholar
  22. 22.
    Xiong Y, Harmon CS (1997) Interleukin-1beta is differentially expressed by human dermal papilla cells in response to PKC activation and is a potent inhibitor of human hair follicle growth in organ culture. J Interferon Cytokine Res 17(3):151–157PubMedCrossRefGoogle Scholar
  23. 23.
    Yang Y, Gil M, Byun SM, Choi I, Pyun KH, Ha H (1996) Transforming growth factor-beta1 inhibits human keratinocyte proliferation by upregulation of a receptor-type tyrosine phosphatase R-PTP-kappa gene expression. Biochem Biophys Res Commun 228:807–812. doi:10.1006/bbrc.1996.1736 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Sungran Huh
    • 1
  • Jongsung Lee
    • 1
  • Eunsun Jung
    • 1
  • Sang-Cheol Kim
    • 2
  • Jung-Il Kang
    • 2
  • Jienny Lee
    • 1
  • Yong-Woo Kim
    • 1
  • Young Kwan Sung
    • 3
  • Hee-Kyoung Kang
    • 2
  • Deokhoon Park
    • 1
  1. 1.Biospectrum Life Science InstituteGyeonggi-doRepublic of Korea
  2. 2.Department of PharmacologyCheju National University School of MedicineJeju CityRepublic of Korea
  3. 3.Department of Immunology, School of MedicineKyungpook National UniversityDaeguRepublic of Korea

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