title: 15-deoxy prostaglandin J2, the nonenzymatic metabolite of prostaglandin D2, induces apoptosis in keratinocytes of human hair follicles: a possible explanation for prostaglandin D2-mediated inhibition of hair growth.
abstract: Recent studies have shown that prostaglandin D2 (PGD2) and its nonenzymatic metabolite, 15-deoxy-Δ(12,14)-prostaglandin J2 (15-dPGJ2), inhibit in vitro growth of explanted human hair follicles and inhibit hair growth in mice through the GPR44 (DP2). However, the underlying mechanism is still unclear. In this study, we first investigated the expression of DP2 in human hair follicles and in cultured follicular cells. We found that DP2 is strongly expressed in the outer root sheath (ORS) cells and weakly expressed in the dermal papilla (DP) cells. We observed slight growth stimulation when ORS and DP cells were treated with PGD2. We also observed slight growth stimulation when DP and ORS cells were treated with low concentrations (0.5 and 1 μM) of 15-dPGJ2. However, 5 μM 15-dPGJ2 inhibited the viability and caused apoptosis of both cell types. Exposure of cultured human hair follicles to 15-dPGJ2 resulted in significant apoptosis in follicular keratinocytes. Altogether, our data provide an evidence that 15-dPGJ2 promotes apoptosis in follicular keratinocytes and provide rationale for developing remedies for the prevention and treatment of hair loss based on DP2 antagonism.
authors.affiliation: Department of Immunology, School of Medicine, Kyungpook National University, 101 Dongin-dong 2 Ga, Jung-gu, Daegu, 700-422, Republic of Korea.
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Joo
authors.affiliation: Department of Immunology, School of Medicine, Kyungpook National University, 101 Dongin-dong 2 Ga, Jung-gu, Daegu, 700-422, Republic of Korea.
authors.forename: Yoo Ri
authors.initials: YR
authors.lastname: Kang
authors.affiliation: Department of Immunology, School of Medicine, Kyungpook National University, 101 Dongin-dong 2 Ga, Jung-gu, Daegu, 700-422, Republic of Korea. go3004@knu.ac.kr.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Kwack
authors.affiliation: Department of Immunology, School of Medicine, Kyungpook National University, 101 Dongin-dong 2 Ga, Jung-gu, Daegu, 700-422, Republic of Korea. ysung@knu.ac.kr.
authors.forename: Young Kwan
authors.initials: YK
authors.lastname: Sung
mesh_terms: D000505:Alopecia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006197:Hair / Q000254:growth & development / Q000378:metabolism; D018859:Hair Follicle / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000633:toxicity; D011971:Receptors, Immunologic / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor
keywords: 15-dPGJ2; Apoptosis; DP2; Follicular keratinocytes; Hair loss; PGD2