Kim Bong-Kyu, Lee Hwa-Young, Kim Injung, Choi Keonwoo, Park Jongkeun, Yoon Sungjoo K
Department of Medical Lifesciences, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Medical Lifesciences, The Catholic University of Korea, Seoul, Republic of Korea.
J Dermatol Sci. 2014 Apr;74(1):81-7. doi: 10.1016/j.jdermsci.2013.12.007. Epub 2014 Jan 2.
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.
To investigate regulation of Dkk1 by HR and its effect on hair formation.
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.
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.
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.
无毛基因（Hr）是一种主要在皮肤中表达的转录共抑制因子，可调节毛囊（HF）形态发生和毛发周期。最近，我们报道了一种新的Hr突变小鼠“毛发稀少”（Hr(Hp)），其杂合状态类似于人类毛发疾病玛丽·安遗传性少毛症（MUHH）。Wnt/β-连环蛋白信号通路对于包括皮肤和毛囊在内的各种成年组织的稳态至关重要。Wnt抑制剂之一Dickkopf（Dkk）作为一种诱导凋亡的生长期诱导剂，在毛发周期中抑制头发生长，导致毛囊减少。
研究HR对Dkk1的调控及其对毛发形成的影响。
采用实时PCR和蛋白质印迹分析，研究毛发周期中(+)/Hr(HP)和Hr(Hp)/Hr(Hp)小鼠中Dkk1的相对表达。进行免疫组织化学以确认(+)/Hr(HP)和Hr(Hp)/Hr(Hp)小鼠毛囊中Dkk1的异常表达。为了确定体外Dkk1表达是否也受HR调控，进行了Hr瞬时转染实验。通过确定毛发周期和测量毛囊长度，鉴定Hr(HP)杂合小鼠毛发周期的改变。
Dkk1在(+)/Hr(HP)和Hr(Hp)/Hr(Hp)小鼠皮肤以及Hr过表达的小鼠角质形成细胞中表达增加。此外，与野生型小鼠相比，观察到(+)/Hr(HP)小鼠的毛囊更早进入退行期且毛囊长度缩短。
研究结果表明，HR上调Dkk1导致Hr(Hp)/Hr(Hp)小鼠毛囊发育异常和毛囊再生失败。这些发现还表明，(+)/Hr(HP)小鼠毛发周期的改变与HR上调Dkk1有关。
