Foxp1 Regulates the Proliferation of Hair Follicle Stem Cells in Response to Oxidative Stress during Hair Cycling.
Foxp1 Regulates the Proliferation of Hair Follicle Stem Cells in Response to Oxidative Stress during Hair Cycling.
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Foxp1 调节毛囊干细胞的增殖以响应毛发循环过程中的氧化应激
DOI：
10.1371/journal.pone.0131674
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Guo X
中科院分区：
文献类型：
--
作者：
Zhao J;Li H;Zhou R;Ma G;Dekker JD;Tucker HO;Yao Z;Guo X
毛囊干细胞（HFSCs）在毛囊生长初期通过有限周期的线性增殖循环生成外根鞘（ORS）。然而，控制HFSC增殖速度的机制仍不清楚。我们发现Foxp1，一个转录因子，随着氧化应激的增加，在从生长期到衰退期的过程中，从细胞核动态地迁移到细胞质中。质谱分析显示Foxp1蛋白的S468磷酸化响应氧化应激并影响其核质易位。毛囊中Foxp1缺失导致ROS积累受损和HFSC增殖增加。此外，NAC处理大大延长了foxp1缺陷背景下的生长持续时间和HFSC增殖。在分子上，Foxp1通过抑制trx1介导的还原功能来增强ROS水平，随后通过调节p19/p53通路的活性来实现细胞周期阻滞。我们的研究结果确定了Foxp1在毛发循环过程中控制HFSC增殖和细胞动态定位中的新作用，以响应氧化应激。
Hair follicle stem cells (HFSCs) in the bugle circularly generate outer root sheath (ORS) through linear proliferation within limited cycles during anagen phases. However, the mechanisms controlling the pace of HFSC proliferation remain unclear. Here we revealed that Foxp1, a transcriptional factor, was dynamically relocated from the nucleus to the cytoplasm of HFSCs in phase transitions from anagen to catagen, coupled with the rise of oxidative stress. Mass spectrum analyses revealed that the S468 phosphorylation of Foxp1 protein was responsive to oxidative stress and affected its nucleocytoplasmic translocation. Foxp1 deficiency in hair follicles led to compromised ROS accrual and increased HFSC proliferation. And more, NAC treatment profoundly elongated the anagen duration and HFSC proliferation in Foxp1-deficient background. Molecularly, Foxp1 augmented ROS levels through suppression of Trx1-mediated reductive function, thereafter imposing the cell cycle arrest by modulating the activity of p19/p53 pathway. Our findings identify a novel role for Foxp1 in controlling HFSC proliferation with cellular dynamic location in response to oxidative stress during hair cycling.