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. 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.