Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes.
Recent studies suggest that androgen-driven alteration to the autocrine and paracrine factors produced by scalp dermal papilla (DP) cells may be a key to androgen-potentiated balding. Here, we screened dihydrotestosterone (DHT)-regulated genes in balding DP cells and found that dickkopf 1 (DKK-1) is one of the most upregulated genes. DKK-1 messenger RNA is upregulated in 3-6 hours after 50-100 nM DHT treatment and ELISA showed that DKK-1 is secreted from DP cells in response to DHT. A co-culture system using outer root sheath (ORS) keratinocytes and DP cells showed that DHT inhibits the growth of ORS cells, and neutralizing antibody against DKK-1 significantly reversed the growth inhibition of ORS cells. Analysis of co-cultured ORS cells showed a significant increment of sub-G1 apoptotic cells in response to DHT. Also, recombinant human DKK-1 inhibited the growth of ORS cells and triggered apoptotic cell death. In addition, DHT-induced epithelial cell death in cultured hair follicles was reversed by neutralizing DKK-1 antibody. Moreover, immunoblotting showed that the DKK-1 level is up in the bald scalp compared with the haired scalp of patients with androgenetic alopecia. Altogether, our data strongly suggest that DHT-inducible DKK-1 is involved in DHT-driven balding.
Kwack
Mi Hee
MH
Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea.
Sung
Young Kwan
YK
Chung
Eun Jung
EJ
Im
Sang Uk
SU
Ahn
Ji Seop
JS
Kim
Moon Kyu
MK
Kim
Jung Chul
JC
D000505:Alopecia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D000728:Androgens / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D018920:Coculture Techniques; D013196:Dihydrotestosterone / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D018859:Hair Follicle / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000276:immunology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques
D000728:Androgens; D000906:Antibodies; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D013196:Dihydrotestosterone