Androgen receptor accelerates premature senescence of human dermal papilla cells in association with DNA damage.
The dermal papilla, located in the hair follicle, expresses androgen receptor and plays an important role in hair growth. Androgen/Androgen receptor actions have been implicated in the pathogenesis of androgenetic alopecia, but the exact mechanism is not well known. Recent studies suggest that balding dermal papilla cells exhibit premature senescence, upregulation of p16(INK4a), and nuclear expression of DNA damage markers. To investigate whether androgen/AR signaling influences the premature senescence of dermal papilla cells, we first compared frontal scalp dermal papilla cells of androgenetic alopecia patients with matched normal controls and observed that premature senescence is more prominent in the dermal papilla cells of androgenetic alopecia patients. Exposure of androgen induced premature senescence in dermal papilla cells from non-balding frontal and transitional zone of balding scalp follicles but not in beard follicles. Overexpression of the AR promoted androgen-induced premature senescence in association with p16(INK4a) upregulation, whereas knockdown of the androgen receptor diminished the effects of androgen. An analysis of γ-H2AX expression in response to androgen/androgen receptor signaling suggested that DNA damage contributes to androgen/androgen receptor-accelerated premature senescence. These results define androgen/androgen receptor signaling as an accelerator of premature senescence in dermal papilla cells and suggest that the androgen/androgen receptor-mediated DNA damage-p16(INK4a) axis is a potential therapeutic target in the treatment of androgenetic alopecia.
Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan ; Graduate Institute of Clinical Medical Sciences, Chang Gung University, College of Medicine, Kaohsiung, Taiwan ; Center for Menopause and Reproductive Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Yi-Chien
YC
Yang
Hung-Chun
HC
Fu
Ching-Yuan
CY
Wu
Kuo-Ting
KT
Wei
Ko-En
KE
Huang
Hong-Yo
HY
Kang
D000328:Adult; D000505:Alopecia / Q000235:genetics / Q000378:metabolism; D000728:Androgens / Q000494:pharmacology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D004249:DNA Damage; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D018859:Hair Follicle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D055815:Young Adult
D000728:Androgens; D011944:Receptors, Androgen