title: A cell-based system for screening hair growth-promoting agents.
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.
authors.affiliation: Biospectrum Life Science Institute, 101-701 SK Ventium, 522 Dangjung Dong, Gunpo City, 435-833 Gyeonggi-do, Republic of Korea.
authors.forename: Sungran
authors.initials: S
authors.lastname: Huh
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
authors.forename: Eunsun
authors.initials: E
authors.lastname: Jung
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Kim
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Kang
authors.forename: Jienny
authors.initials: J
authors.lastname: Lee
authors.forename: Yong-Woo
authors.initials: YW
authors.lastname: Kim
authors.forename: Young Kwan
authors.initials: YK
authors.lastname: Sung
authors.forename: Hee-Kyoung
authors.initials: HK
authors.lastname: Kang
authors.forename: Deokhoon
authors.initials: D
authors.lastname: Park
mesh_terms: D000505:Alopecia / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D000818:Animals; D047310:Apigenin / Q000494:pharmacology; D018929:Cell Culture Techniques; D048708:Cell Growth Processes / Q000187:drug effects / Q000276:immunology; D003474:Curcumin / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004817:Epidermis / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006197:Hair / Q000187:drug effects / Q000254:growth & development / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D051381:Rats; D015533:Transcriptional Activation / Q000187:drug effects / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014738:Vibrissae / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D053773:Transforming Growth Factor beta1; D047310:Apigenin; D003474:Curcumin