Inflammatory mediator TAK1 regulates hair follicle morphogenesis and anagen induction shown by using keratinocyte-specific TAK1-deficient mice.
Inflammatory mediator TAK1 regulates hair follicle morphogenesis and anagen induction shown by using keratinocyte-specific TAK1-deficient mice.
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DOI：
10.1371/journal.pone.0011275
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发表时间：
2010-06-23
期刊：
影响因子：
3.7
通讯作者：
Hashimoto K
中科院分区：
文献类型：
--
作者：
Sayama K;Kajiya K;Sugawara K;Sato S;Hirakawa S;Shirakata Y;Hanakawa Y;Dai X;Ishimatsu-Tsuji Y;Metzger D;Chambon P;Akira S;Paus R;Kishimoto J;Hashimoto K
转化生长因子-β-激活的蛋白1(Tak1)是核因子-κB途径中的一员，调节炎症反应。我们以前发现，TAK1还调节角质形成细胞的生长、分化和凋亡。然而，目前尚不清楚TAK1是否在上皮-间充质相互作用中起作用。为了检验这种可能性，我们研究了TAK1在小鼠毛囊发育和周期中的作用，作为一个有指导意义的模型系统。通过比较角质形成细胞特异性TAK1缺陷小鼠(Map3k7fl/flK5-Cre)和对照组小鼠，我们发现在胚胎15.5d，Map3k7fl/flK5-Cre小鼠的毛囊前体细胞数量显著减少，随后的毛囊形态发生受阻。接下来，我们通过分析三苯氧胺诱导的角质形成细胞特异性TAK1缺乏症小鼠的毛发周期进程(Map3k7f1/flK14-CRE-ERT2)，分析了TAK1在毛囊周期重塑中的作用。脱毛诱导毛发生长活跃后，局部应用他莫昔芬可去除TAK1。这导致TAK1基因缺陷小鼠的生长期发育明显受阻。在已经处于生长期的毛囊中TAK1的缺失导致了过早的、由细胞凋亡驱动的毛囊退化，并伴随着毛囊的损伤。这些研究首次证明，炎症介质TAK1调节毛囊的诱导和形态发生，是生长期诱导和生长期维持所必需的。
Transforming growth factor-β-activated kinase 1 (TAK1) is a member of the NF-κB pathway and regulates inflammatory responses. We previously showed that TAK1 also regulates keratinocyte growth, differentiation, and apoptosis. However, it is unknown whether TAK1 has any role in epithelial–mesenchymal interactions. To examine this possibility, we studied the role of TAK1 in mouse hair follicle development and cycling as an instructive model system. By comparing keratinocyte-specific TAK1-deficient mice (Map3k7 fl/flK5-Cre) with control mice, we found that the number of hair germs (hair follicles precursors) in Map3k7 fl/flK5-Cre mice was significantly reduced at E15.5, and that subsequent hair follicle morphogenesis was retarded. Next, we analyzed the role of TAK1 in the cyclic remodeling in follicles by analyzing hair cycle progression in mice with a tamoxifen-inducible keratinocyte-specific TAK1 deficiency (Map3k7 fl/flK14-Cre-ERT2). After active hair growth (anagen) was induced by depilation, TAK1 was deleted by topical tamoxifen application. This resulted in significantly retarded anagen development in TAK1-deficient mice. Deletion of TAK1 in hair follicles that were already in anagen induced premature, apoptosis-driven hair follicle regression, along with hair follicle damage. These studies provide the first evidence that the inflammatory mediator TAK1 regulates hair follicle induction and morphogenesis, and is required for anagen induction and anagen maintenance.
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影响因子：
3.5
作者：
Pispa, Johanna;Pummila, Marja;Mikkola, Marja L.
通讯作者：
Mikkola, Marja L.
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Metzger, D
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