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Tafluprost, A Prostaglandin F2α Analog, Has Therapeutic Potential For Androgenic Alopecia Through Modulation Of Hair Cycle
Kahori Kinoshita, M.D.1, Harunosuke Kato, M.D.1, Hiroko Takada, PhD2, Koji Kanayama, M.D.1, Takanobu Mashiko, M.D.1, Kenzo Koike, PhD3, Akira Kurisaki, PhD2, Satoshi Itami, M.D.4, Kotaro Yoshimura, M.D.5.
1Department of Plastic Surgery, The university of Tokyo, Tokyo, Japan, 2Research Center for Stem Cell Engineering, National Institute for Advanced Industrial Science and Technology, Ibaraki, Japan, 3Beauty Research Center, KAO Corp., Tokyo, Japan, 4Department of Regenerative Dermatology, Osaka University, Osaka, Japan, 5Department of Plastic Surgery,The university of Tokyo, Jichi Medical University, Tokyo, Tochigi, Japan.

PURPOSE:
Topical prostaglandin(PG) F2α was recently reported to promote hair growth and a new PGF2α analog, tafluprost, was investigated in this study.
METHODS:
Topical tafluprost was applied once daily on either telogen skin or depilation-induced anagen skin in C57BL/6 mice using 7 different concentrations, and hair growth was evaluated until Day 42. The underlying mechanism was explored by various in vitro and in vivo approaches.
RESULTS:
Tafluprost application on telogen skin promoted telogen-to-anagen conversion most at the same concentration as a commercial eye-drop. Hair protrusion was observed much earlier(Day 19.6±0.7) than control(Day 42). In depilation-induced anagen mice, tafluprost elongated early anagen phase, but didn’t elongate mid-late anagen phase. In organ culture of human scalp hair and mice vibrissa follicles, hair growth wasn’t accelerated by tafluprost, and proliferation of cultured human dermal papilla cells(hDPCs) wasn’t affected by tafluprost in BrdU-incorporation analysis. Chick chorioallantoic membrane assay showed no promotion of angiogenesis by tafluprost. Microarray using hDPCs and human keratinocytes(hKCs) showed that IL-1β, known to induce catagen, and inflammatory cytokines such as IL-6, IL-8 and CXCL2 were downregulated in tafluporst-treated hDPCs, whereas hair-cycle-associated growth factors such as FGF-1, 2, and 7 were stable. Genes related to keratinization were upregulated in hKCs. The correlation between PGF2α, PGD2 and PGE2 was also evaluated in gene expression using real time PCR, indicating the affected profile of these genes.
CONCLUSION:
Tafluprost affected function of hDPCs and hKCs and showed therapeutic potentials for androgenic alopecia by modulating hair cycle such as anagen induction and elongation of early anagen.


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