Coactivator MED1 ablation in keratinocytes results in hair-cycling defects and epidermal alterations.
Coactivator MED1 ablation in keratinocytes results in hair-cycling defects and epidermal alterations.
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DOI：
10.1038/jid.2011.430
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发表时间：
2012-04
影响因子：
6.5
通讯作者：
Bikle, Daniel D.
中科院分区：
文献类型：
--
作者：
Oda, Yuko;Hu, Lizhi;Bul, Vadim;Elalieh, Hashem;Reddy, Janardan K.;Bikle, Daniel D.
转录辅激活因子复合物介体促进核激素受体和其他转录因子的转录。我们先前已经从原代角质形成细胞中分离出了作为维生素D受体相互作用蛋白复合物的介体复合物。我们鉴定了介体在培养的角质形成细胞中角质形成细胞增殖和分化中的作用。在这里，我们通过产生条件无效小鼠来研究介体的体内作用，其中介体复合物的关键亚基MED 1从其角质形成细胞中缺失。MED 1消融导致毛发分化和周期异常，导致脱发。在第一个毛囊周期中，MED 1缺失导致毛囊快速退化。毛发分化减少，β-连环蛋白/维生素D受体（VDR）调节的基因表达显著降低。在随后的成年毛发周期中，MED 1消融激活了毛囊周期的启动。Shh信号增加，但终末分化不足。MED 1的缺失还引起毛囊间表皮角质形成细胞的过度增殖，并增加表皮分化标志物的表达。这些结果表明MED 1在调节毛发/表皮增殖和分化中起关键作用。
The transcriptional coactivator complex Mediator facilitates transcription of nuclear hormone receptors and other transcription factors. We have previously isolated the Mediator complex from primary keratinocytes as the vitamin D receptor interacting protein complex. We identified a role for Mediator in keratinocyte proliferation and differentiation in cultured keratinocytes. Here, we investigated the in vivo role of Mediator by generating conditional null mice, where a critical subunit of the Mediator complex, MED1, is deleted from their keratinocytes. The MED1 ablation resulted in aberrant hair differentiation and cycling leading to hair loss. During the first hair follicle cycle, MED1 deletion resulted in a rapid regression of the hair follicles. Hair differentiation was reduced, and β-catenin/vitamin D receptor (VDR) regulated gene expression was dramatically decreased. In the subsequent adult hair cycle, MED1 ablation activated the initiation of hair follicle cycling. Shh signaling was increased, but terminal differentiation was not sufficient. Deletion of MED1 also caused hyper-proliferation of interfollicular epidermal keratinocytes, and increased the expression of epidermal differentiation markers. These results indicate that MED1 plays a critical role in regulating hair/epidermal proliferation and differentiation.
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影响因子：
6.5
作者：
Hawker, Nathaniel P.;Pennypacker, Sally D.;Bikle, Daniel D.
通讯作者：
Bikle, Daniel D.
影响因子：
6.5
作者：
Ellison, Tara I.;Smith, Molly K.;MacDonald, Paul N.
通讯作者：
MacDonald, Paul N.
影响因子：
16
作者：
Deato, Maria Divina E.;Marr, Michael T.;Sottero, Theo;Inouye, Carla;Hu, Ping;Tjian, Robert
通讯作者：
Tjian, Robert
影响因子：
3.7
作者：
Pálmer HG;Anjos-Afonso F;Carmeliet G;Takeda H;Watt FM
通讯作者：
Watt FM
影响因子：
64.8
作者：
Rachez, C;Lemon, BD;Freedman, LP
通讯作者：
Freedman, LP