Increased expression of Dkk1 by HR is associated with alteration of hair cycle in hairpoor mice

Abstract

BackgroundHairless (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” (HrHp), 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. ObjectiveTo investigate regulation of Dkk1 by HR and its effect on hair formation. MethodsThe relative expression of Dkk1 in +/HrHP and HrHp/HrHp 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 +/HrHP and HrHp/HrHp 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 HrHP heterozygous mice was identified by determination of the hair cycle and measurement of HF length. ResultsDkk1 expression was increased in the skin of +/HrHP and HrHp/HrHp mice, as well as in Hr-overexpressing mouse keratinocytes. Additionally, an earlier entrance of HFs into catagen and shortened HF length in +/HrHP mice compared to wild-type mice was observed. ConclusionStudy results suggested that up-regulation of Dkk1 by HR contributed to abnormal development of HFs and failure in regeneration of HFs in HrHp/HrHp mice. These findings also indicated that alteration of the hair cycle in +/HrHP mice was related to the up-regulation of Dkk1 by HR.