Activation of NLRP3 signalling accelerates skin wound healing
Activation of NLRP3 signalling accelerates skin wound healing
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DOI：
10.1111/exd.13441
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发表时间：
2018-01-01
影响因子：
3.6
通讯作者：
Seishima, Mitsuru
中科院分区：
文献类型：
--
作者：
Ito, Hiroyasu;Kanbe, Ayumu;Seishima, Mitsuru
皮肤创伤愈合的过程包括以下三个步骤：炎症、组织形成和组织重塑。这些最佳步骤是正常伤口愈合所需的。最近的报道表明，炎性小体参与先天性免疫反应。在本研究中，我们研究了炎症小体的激活是否影响皮肤创伤修复的过程。使用野生型（WT）、NACHT、LRR和PYD含结构域蛋白3（NALP 3）敲除（KO）和ASC-KO小鼠建立皮肤伤口修复模型。每隔一天观察伤口，并使用摄影计算伤口大小随时间的变化。与WT小鼠相比，NALP 3-KO和ASC-KO小鼠的伤口修复显著受损。NALP 3的抑制剂异甘草素降低WT小鼠的伤口修复速率。与WT小鼠相比，NALP 3-KO小鼠伤口部位中促炎细胞因子的mRNA表达显著降低。用NALP 3的配体三磷酸腺苷（ATP）治疗，上调了伤口部位促炎细胞因子的mRNA表达，并加速了WT小鼠的伤口愈合。划痕试验表明，ATP加速了WT小鼠的小鼠胚胎成纤维细胞的伤口闭合，但对NALP 3-KO小鼠的伤口闭合没有影响。总之，本研究表明，NALP 3途径激活参与伤口修复，局部使用ATP可能是一种有效的治疗方法，可加速伤口愈合。
The process of skin wound healing involves the following three steps: inflammation, tissue formation and tissue remodelling. These optimal steps are required for the development of normal wound healing. Recent reports demonstrated that inflammasomes are involved in the innate immune response. In the present study, we examined whether the activation of inflammasomes affects the process of skin wound repair. The skin wound repair model was established using wild-type (WT), NACHT, LRR and PYD domains-containing protein 3 (NALP3) knockout (KO) and ASC-KO mice. The wounds were observed every other day, and changes in wound size over time were calculated using photography. Wound repair in NALP3-KO and ASC-KO mice was significantly impaired compared with WT mice. Isoliquiritigenin, an inhibitor of NALP3, decreased the rate of wound repair in WT mice. mRNA expression of pro-inflammatory cytokines in the wound sites of NALP3-KO mice was markedly decreased compared with WT mice. Treatment with adenosine triphosphate (ATP), a ligand of NALP3, upregulated the mRNA expression of pro-inflammatory cytokines at the wound site and accelerated wound healing in the WT mice. Scratch assay revealed that ATP accelerated wound closure in mouse embryonic fibroblasts from WT mice but not from NALP3-KO mice. In conclusion, the present study demonstrated that NALP3 pathway activation is involved in wound repair, and the topical use of ATP may be useful as an effective treatment for accelerating wound healing.