MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway.

MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway.
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DOI:
10.1083/jcb.201404001
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发表时间:
2014-11-24
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Botchkareva NV
Botchkareva NV
中科院分区:
其他
文献类型:
--
作者:
Ahmed MI;Alam M;Emelianov VU;Poterlowicz K;Patel A;Sharov AA;Mardaryev AN;Botchkareva NV

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miRNA-214通过靶向β-catenin调节毛囊发育和周期,从而调节Wnt通路的转导。皮肤发育受基因激活和沉默的复杂程序控制,包括基因表达的microRNA依赖性调节。在这里,我们发现miR-214通过靶向β-catenin(Wnt信号通路的关键组分)调节皮肤形态发生和毛囊(HF)周期。miR-214在皮肤上皮中表现出不同的表达模式,其在角质形成细胞中的诱导性过表达抑制增殖,这导致较少的HF形成,毛球大小减小,毛发产生变薄。miR-214对HF发展和循环的抑制作用与多种信号传导途径的活性改变相关,包括关键Wnt信号传导介质β-catenin和Lef-1的表达降低,并通过药理学Wnt激活剂治疗来挽救。最后,我们确定β-catenin是角质形成细胞中保守的miR-214靶标之一。这些数据为进一步分析miR-214作为正常组织稳态、再生和衰老过程中Wnt通路活性和干细胞功能的关键调节因子提供了重要基础。
miRNA-214 regulates hair follicle development and cycling by targeting β-catenin and thereby modulating Wnt pathway transduction. Skin development is governed by complex programs of gene activation and silencing, including microRNA-dependent modulation of gene expression. Here, we show that miR-214 regulates skin morphogenesis and hair follicle (HF) cycling by targeting β-catenin, a key component of the Wnt signaling pathway. miR-214 exhibits differential expression patterns in the skin epithelium, and its inducible overexpression in keratinocytes inhibited proliferation, which resulted in formation of fewer HFs with decreased hair bulb size and thinner hair production. The inhibitory effects of miR-214 on HF development and cycling were associated with altered activities of multiple signaling pathways, including decreased expression of key Wnt signaling mediators β-catenin and Lef-1, and were rescued by treatment with pharmacological Wnt activators. Finally, we identify β-catenin as one of the conserved miR-214 targets in keratinocytes. These data provide an important foundation for further analyses of miR-214 as a key regulator of Wnt pathway activity and stem cell functions during normal tissue homeostasis, regeneration, and aging.
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