JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing.
JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing.
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DOI：
10.1038/s41598-017-06750-7
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发表时间：
2017-07-26
影响因子：
4.6
通讯作者：
Ju BG
中科院分区：
文献类型：
--
作者：
Na J;Shin JY;Jeong H;Lee JY;Kim BJ;Kim WS;Yune TY;Ju BG
研究表明，表观遗传调控在皮肤创伤愈合中起着重要作用。我们先前发现组蛋白H3K27me3去甲基化酶JMJD3调节角质形成细胞伤口愈合中的炎症和细胞迁移。在这项研究中，我们使用体外细胞和体内动物模型鉴定了Notch1作为创伤角质形成细胞中JMJD3和NF-κ B的直接靶点。我们发现Notch1在创伤边缘表达上调，其表达依赖于创伤角质形成细胞中的JMJD 3和NF-κ B。我们还发现Notch1激活RhoU和PLAU基因的表达，这是细胞迁移的关键调节因子。一致地，Notch1的缺失或失活导致丝状伪足形成减少，粘着斑和肌动蛋白应力纤维增加，导致角质形成细胞迁移减少和皮肤伤口愈合。因此，我们的研究结果提供了角质形成细胞伤口愈合中涉及JMJD3/NF-κ B-Notch通路的分子机制。
It has been shown that epigenetic regulation plays an important role in skin wound healing. We previously found that histone H3K27me3 demethylase JMJD3 regulates inflammation and cell migration in keratinocyte wound healing. In this study, we identified Notch1 as a direct target of JMJD3 and NF-κB in wounded keratinocytes using in vitro cell and in vivo animal models. We found that Notch1 is up-regulated in the wound edge and its expression is dependent on JMJD3 and NF-κB in wounded keratinocytes. We also found that Notch1 activates the expression of RhoU and PLAU gene, which are critical regulators of cell migration. Consistently, depletion or inactivation of Notch1 resulted in decreased filopodia formation, increased focal adhesion and actin stress fiber, leading to reduced keratinocyte migration and skin wound healing. Thus, our findings provide the molecular mechanism involving JMJD3/NF-κB-Notch pathway in keratinocyte wound healing.
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影响因子：
4
作者：
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通讯作者：
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影响因子：
8
作者：
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影响因子：
10.5
作者：
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通讯作者：
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影响因子：
15.9
作者：
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通讯作者：
Powell, Marianne Broome
DOI：
10.1158/1078-0432.ccr-08-1631
发表时间：
2009-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Bin Hafeez B;Adhami VM;Asim M;Siddiqui IA;Bhat KM;Zhong W;Saleem M;Din M;Setaluri V;Mukhtar H
通讯作者：
Mukhtar H