Mammalian target of rapamycin complex 1 (mTORC1) may modulate the timing of anagen entry in mouse hair follicles
Mammalian target of rapamycin complex 1 (mTORC1) may modulate the timing of anagen entry in mouse hair follicles
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DOI：
10.1111/exd.12062
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发表时间：
2013-01-01
影响因子：
3.6
通讯作者：
Tauchi, Miyuki
中科院分区：
文献类型：
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作者：
Kellenberger, Antonia J.;Tauchi, Miyuki
哺乳动物雷帕霉素靶蛋白（mTOR）是细胞增殖和存活的中心调节因子。有有限的证据表明mTOR影响毛囊（HFs），毛囊经历静止（休止），生长（生长期）和退化（退行期）的周期。我们试图通过体内生化、免疫组织化学和功能方法来研究mTOR，特别是mTOR复合物1 （mTORC1）是否调节头发生长周期。在这里，我们证明了mTORC1激酶活性的定量分析显示了相依赖性的变化，并且S2448磷酸化的mTOR （p-mTOR）以相依赖性的方式定位于HFs的某些位点。这些结果表明mTOR在头发生长起始中的作用。最后，在体内使用特异性mTORC1抑制剂雷帕霉素的药理学挑战中，毛发周期的开始被推迟，这表明mTORC1在新生细胞进入过程中具有功能相关性。基于我们的研究结果，我们提出mTORC1可能参与头发周期的调节，即生长起始的时间。
Mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation and survival. There is limited evidence that mTOR influences hair follicles (HFs), which undergo cycles of quiescence (telogen), growth (anagen) and regression (catagen). We sought to investigate whether mTOR, in particular mTOR complex 1 (mTORC1), regulates the hair growth cycle by employing biochemical, immunohistochemical and functional approaches in vivo. Here, we demonstrate that quantitative analysis of mTORC1 kinase activity shows phase-dependent changes, and phosphorylated mTOR at S2448 (p-mTOR) was localized in certain sites of HFs in a phase-dependent manner. These results were indicative of mTOR's role in hair growth initiation. Finally, in a pharmacological challenge in vivo using the specific mTORC1 inhibitor, rapamycin, hair cycle initiation was delayed, suggesting a functional relevance of mTORC1 in anagen entry. Based on our findings, we propose that mTORC1 may participate in hair cycle regulation, namely the timing of anagen initiation.