Increased expression of Dkk1 by HR is associated with alteration of hair cycle in hairpoor mice.
BACKGROUND
Hairless (Hr), a transcriptional corepressor expressed mainly in the skin, regulates hair follicle (HF) morphogenesis and hair cycling. Recently, we reported a new Hr mutant mouse, "Hairpoor" (Hr(Hp)), that resembles the human hair disorder Marie Unna hereditary hypotrichosis (MUHH) in the heterozygous state. The Wnt/β-catenin signaling pathway is critical for homeostasis in various adult tissues including skin and HFs. One of the Wnt inhibitors, Dickkopf (Dkk), inhibits hair growth during the hair cycle as a catagen inducer of apoptosis, resulting in HF reductions.


OBJECTIVE
To investigate regulation of Dkk1 by HR and its effect on hair formation.


METHODS
The relative expression of Dkk1 in (+)/Hr(HP) and Hr(Hp)/Hr(Hp) mice during the hair cycle was investigated using real time PCR and Western blot analysis. Immunohistochemistry was performed in order to confirm abnormal expression of Dkk1 in HFs of (+)/Hr(HP) and Hr(Hp)/Hr(Hp) mice. To determine whether Dkk1 expression was also regulated by HR in vitro, an Hr-transient transfection experiment was performed. Alteration of the hair cycle in Hr(HP) heterozygous mice was identified by determination of the hair cycle and measurement of HF length.


RESULTS
Dkk1 expression was increased in the skin of (+)/Hr(HP) and Hr(Hp)/Hr(Hp) mice, as well as in Hr-overexpressing mouse keratinocytes. Additionally, an earlier entrance of HFs into catagen and shortened HF length in (+)/Hr(HP) mice compared to wild-type mice was observed.


CONCLUSIONS
Study results suggested that up-regulation of Dkk1 by HR contributed to abnormal development of HFs and failure in regeneration of HFs in Hr(Hp)/Hr(Hp) mice. These findings also indicated that alteration of the hair cycle in (+)/Hr(HP) mice was related to the up-regulation of Dkk1 by HR.
Department of Medical Lifesciences, The Catholic University of Korea, Seoul, Republic of Korea.
Bong-Kyu
BK
Kim
Department of Medical Lifesciences, The Catholic University of Korea, Seoul, Republic of Korea.
Hwa-Young
HY
Lee
Department of Medical Lifesciences, The Catholic University of Korea, Seoul, Republic of Korea.
Injung
I
Kim
Department of Medical Lifesciences, The Catholic University of Korea, Seoul, Republic of Korea.
Keonwoo
K
Choi
Department of Medical Lifesciences, The Catholic University of Korea, Seoul, Republic of Korea.
Jongkeun
J
Park
Department of Medical Lifesciences, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: sjkyoon@catholic.ac.kr.
Sungjoo K
SK
Yoon
D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D018859:Hair Follicle / Q000502:physiology*; D006579:Heterozygote; D006706:Homeostasis; D007039:Hypotrichosis / Q000151:congenital / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D008822:Mice, Transgenic; D012038:Regeneration; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism
C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051176:beta Catenin
Dkk1; HR; Hair cycle; Hairpoor; Wnt pathway