JAM-A knockdown accelerates the proliferation and migration of human keratinocytes, and improves wound healing in rats via FAK/Erk signaling.
JAM-A knockdown accelerates the proliferation and migration of human keratinocytes, and improves wound healing in rats via FAK/Erk signaling.
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JAM-A 敲低可加速人角质形成细胞的增殖和迁移，并通过 FAK/Erk 信号传导改善大鼠伤口愈合
DOI：
10.1038/s41419-018-0941-y
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发表时间：
2018-08-28
影响因子：
9
通讯作者：
Fu X
中科院分区：
文献类型：
--
作者：
Wang Y;Zheng J;Han Y;Zhang Y;Su L;Hu D;Fu X
交界性黏附分子-A(JAM-A)属于免疫球蛋白超家族，主要存在于上皮细胞和内皮细胞的紧密连接处。JAM-A是已知的调节白细胞跨内皮细胞迁移的因子，然而，它如何影响伤口愈合过程中的两个重要步骤--角质形成细胞的增殖和迁移--的研究较少。在本研究中，我们发现JAM-A在正常皮肤表皮中显著表达。RNAi介导的JAM-A基因敲除可显著促进角质形成细胞的增殖和迁移。我们还发现，JAM-A的缺失增加了p-FAK、p-ERK1/2和p-JNK的蛋白水平，而FAK抑制剂PF-562271抑制了JAM-A RNAi上调的p-FAK和p-ERK1/2的表达，而不抑制p-JNK的表达，并减缓了角质形成细胞的增殖和迁移。最后，在大鼠创伤模型中，我们发现JAM-A的缺失显著促进了伤口的愈合过程，而使用PF-562271或ERK1/2抑制剂PD98059则抑制了这些作用。这些结果表明，抑制JAM-A的表达可以促进角质形成细胞的增殖和迁移，并可能通过FAK/ERK途径加速大鼠皮肤创面的愈合过程，提示JAM-A可能成为治疗慢性难治性创面的潜在靶点。
Junctional adhesion molecule-A (JAM-A) belongs to the immunoglobulin superfamily, it predominantly exists at the tight junctions of epithelial and endothelial cells. JAM-A is known to regulate leukocyte trans-endothelial migration, however, how it affects the proliferation and migration of keratinocytes, the two essential steps during wound healing, has less been explored. In this study, we showed that JAM-A was significantly expressed in normal skin epidermis. RNAi-mediated JAM-A knockdown remarkably promoted the proliferation and migration of keratinocytes. We also found that loss of JAM-A increased the protein levels ofp-FAK,p-Erk1/2, andp-JNK; however, FAK inhibitor PF-562271 restrained the expression ofp-FAK andp-Erk1/2 elevated by JAM-A RNAi, but notp-JNK, and also slowed down keratinocyte proliferation and migration. Finally, in a rat wound model we showed that absence of JAM-A significantly promoted the wound healing process, while the use of PF-562271 or Erk1/2 inhibitor PD98059 repressed those effects. These data collectively demonstrate that suppressing JAM-A expression could promote the proliferation and migration of keratinocytes and accelerate the healing process of rat skin wounds, potentially via FAK/Erk pathway, indicating that JAM-A might serve as a potential therapeutic target for the treatment of chronic refractory wounds.
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影响因子：
30.5
作者：
Ostermann, G;Weber, KSC;Weber, C
通讯作者：
Weber, C
影响因子：
4.8
作者：
Fitsialos, Giorgos;Chassot, Anne-Amandine;Ponzio, Gilles
通讯作者：
Ponzio, Gilles
影响因子：
4.1
作者：
NAIK, UP;EHRLICH, YH;KORNECKI, E
通讯作者：
KORNECKI, E
影响因子：
5.6
作者：
Huh, Jeong-Eun;Nam, Dong-Woo;Lee, Jae-Dong
通讯作者：
Lee, Jae-Dong
影响因子：
6
作者：
Lai, I-Rue;Chu, Pei-Yu;Shen, Tang-Long
通讯作者：
Shen, Tang-Long