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.
Conclusion: 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.
Keywords: Dkk1; HR; Hair cycle; Hairpoor; Wnt pathway.
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