JMJD3 和 NF-κB 依赖性的 Notch1 基因激活是皮肤创伤愈合过程中角质细胞迁移所必需的。
JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing.
机构信息
Department of Life Science, Sogang University, Seoul, 04107, Korea.
Department of Dermatology, College of Medicine, Chung-Ang University, Seoul, 06973, Korea.
出版信息
Sci Rep. 2017 Jul 26;7(1):6494. doi: 10.1038/s41598-017-06750-7.
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.
已经表明，表观遗传调控在皮肤伤口愈合中起着重要作用。我们之前发现组蛋白 H3K27me3 去甲基酶 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 是 JMJD3 和 NF-κB 在受伤角质形成细胞中的直接靶标。我们发现 Notch1 在伤口边缘上调，其表达依赖于 JMJD3 和 NF-κB 在受伤角质形成细胞中的表达。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剂。一致地，Notch1 的耗竭或失活导致丝状伪足形成减少，焦点黏附增加和肌动蛋白应力纤维增加，导致角质形成细胞迁移和皮肤伤口愈合减少。因此，我们的研究结果提供了涉及角质形成细胞伤口愈合的 JMJD3/NF-κB-Notch 通路的分子机制。
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