title: Dickkopf 1 promotes regression of hair follicles.
abstract: Recently, we suggested that Dickkopf 1 (DKK-1) is a pathogenic mediator involved in male pattern baldness. As premature catagen onset is a key characteristic of male pattern baldness, in this study, we evaluated whether DKK-1 has a role as a catagen inducer in hair cycling. Herein, we report that recombinant human DKK-1 (rhDKK-1) injection into the hypodermis of mice during anagen caused premature onset of catagen, whereas neutralizing DKK-1 antibody delayed anagen-to-catagen transition in mice. Moreover, treatment with rhDKK-1 led to a decrease in final hair follicle length, whereas DKK-1 antibody led to an increase compared with control animals. In addition, DKK-1 and DKK-1 messenger RNA expression is most upregulated in follicular keratinocytes of late anagen in depilation-induced hair cycle progression. Moreover, we observed that rhDKK-1 blocks canonical Wnt-mediated activation of β-catenin signaling and induces the proapoptotic protein Bax, resulting in apoptosis in outer root sheath keratinocytes. Taken together, our data strongly suggest that DKK-1 is involved in anagen-to-catagen transition in the hair cycle by regulating the activity of follicular keratinocytes.
authors.affiliation: Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Mi H
authors.initials: MH
authors.lastname: Kwack
authors.forename: Moon K
authors.initials: MK
authors.lastname: Kim
authors.forename: Jung C
authors.initials: JC
authors.lastname: Kim
authors.forename: Young K
authors.initials: YK
authors.lastname: Sung
mesh_terms: D000505:Alopecia / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D006197:Hair / Q000187:drug effects / Q000254:growth & development / Q000637:transplantation; D018859:Hair Follicle / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D006801:Humans; D007271:Injections, Intradermal; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; C494827:Bax protein, mouse; C495267:CTNNB1 protein, mouse; C501126:DKK1 protein, human; C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051153:Wnt Proteins; D051028:bcl-2-Associated X Protein; D051176:beta Catenin