Involvement of the Edar signaling in the control of hair follicle involution (catagen)
Involvement of the Edar signaling in the control of hair follicle involution (catagen)
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DOI：
10.2353/ajpath.2006.060227
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发表时间：
2006-12-01
影响因子：
6
通讯作者：
Botchkarev, Vladimir A.
中科院分区：
文献类型：
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作者：
Fessing, Michael Y.;Sharova, Tatyana Y.;Botchkarev, Vladimir A.
外胚层发育异常蛋白（Ectodysplasin，Eda）及其受体（Edar）是毛囊等多种外胚层衍生物正常发育所必需的。在这里，我们表明，在小鼠毛发周期中，Eda A1，Edar，Edaradd和TRAF6转录物的表达在静息期最小，在HF从活跃生长到消退（退化期）的过渡期间最大。Eda A1 mRNA和Edar蛋白在生长期HFs的毛基质和外根鞘和内根鞘中表达。在退化期，Eda A1 mRNA和Edar蛋白在外根鞘和内根鞘中表达，随后在次生毛胚中表达。与相应的对照组相比，无绒毛小鼠或野生型小鼠经抑制Edar信号传导的融合蛋白治疗后，退行期发育伴随外根鞘细胞凋亡增加显著加速。微阵列，实时聚合酶链反应，和免疫组化分析的无绒毛小鼠的皮肤显示，与对照组相比，X连锁的凋亡抑制蛋白（XIAP）的表达强烈下降，这表明XIAP作为Edar信号的目标。因此，我们的数据表明，除了其在HF形态发生中的既定作用外，Edar信号传导还参与毛发周期控制并调节退行期HF角质形成细胞的凋亡。
Ectodysplasin (Eda) and its receptor (Edar) are required for normal development of several ectodermal derivatives including hair follicles (HFs). Here, we show that during the murine hair cycle the expression of Eda A1, Edar, Edaradd, and TRAF6 transcripts are minimal in the resting phase and maximal during HF transition from active growth to regression (catagen). Eda A1 mRNA and Edar proteins were expressed in the hair matrix and outer and inner root sheaths of anagen HFs. During catagen, Eda A1 mRNA and Edar protein were expressed in the outer and inner root sheaths and later in the secondary hair germ. Catagen development accompanied by increased apoptosis in the outer root sheath was significantly accelerated in downless mice or after treatment of wild-type mice by a fusion protein that inhibits Edar signaling, compared with the corresponding controls. Microarray, real-time polymerase chain reaction, and immunohistochemical analyses of skin of downless mice revealed a strong decrease of expression of X-linked inhibitor of apoptosis protein (XIAP), compared with the controls, suggesting XIAP as a target for Edar signaling. Thus, our data demonstrate that in addition to its well-established role in HF morphogenesis, Edar signaling is also involved in hair cycle control and regulates apoptosis in HF keratinocytes during catagen.