Sphingosine-1-Phosphate Facilitates Skin Wound Healing by Increasing Angiogenesis and Inflammatory Cell Recruitment with Less Scar Formation
Sphingosine-1-Phosphate Facilitates Skin Wound Healing by Increasing Angiogenesis and Inflammatory Cell Recruitment with Less Scar Formation
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DOI：
10.3390/ijms20143381
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发表时间：
2019-07-02
影响因子：
5.6
通讯作者：
Takabe, Kazuaki
中科院分区：
文献类型：
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作者：
Aoki, Masayo;Aoki, Hiroaki;Takabe, Kazuaki
伤口愈合始于分泌伤口相关因子的炎症细胞的募集。此步骤之后是成纤维细胞激活和组织构建。 1-磷酸鞘氨醇 (S1P) 是一种脂质介质，可促进血管生成、细胞增殖并吸引免疫细胞。我们通过改变其生物酶鞘氨醇激酶 1 (SphK1) 的表达来研究 S1P 在皮肤伤口愈合中的作用。使用小鼠切除伤口夹板模型。鞘氨醇激酶-1 (SphK1) 在小鼠伤口中高度表达，SphK1-/- 小鼠表现出伤口闭合延迟以及血管生成和炎症细胞募集减少。纳米颗粒介导的局部 SphK1 过度表达可加速伤口闭合，这与血管生成、炎症细胞募集和各种伤口相关因素的增加有关。 SphK1的过表达也导致疤痕减少，转化生长因子（TGF）-（31和S1P受体2（S1PR2）信号之间的相互作用可能发挥关键作用。总之，SphK1在增强免疫力方面发挥着重要作用，并有助于早期伤口愈合并抑制疤痕形成。S1P可以成为外科、创伤和慢性伤口处理中具有抗疤痕作用的新型治疗分子。
Wound healing starts with the recruitment of inflammatory cells that secrete wound-related factors. This step is followed by fibroblast activation and tissue construction. Sphingosine-1-phosphate (S1P) is a lipid mediator that promotes angiogenesis, cell proliferation, and attracts immune cells. We investigated the roles of S1P in skin wound healing by altering the expression of its biogenic enzyme, sphingosine kinase-1 (SphK1). The murine excisional wound splinting model was used. Sphingosine kinase-1 (SphK1) was highly expressed in murine wounds and that SphK1-/- mice exhibit delayed wound closure along with less angiogenesis and inflammatory cell recruitment. Nanoparticle-mediated topical SphK1 overexpression accelerated wound closure, which associated with increased angiogenesis, inflammatory cell recruitment, and various wound-related factors. The SphK1 overexpression also led to less scarring, and the interaction between transforming growth factor (TGF)-(31 and S1P receptor-2 (S1PR2) signaling is likely to play a key role. In summary, SphK1 play important roles to strengthen immunity, and contributes early wound healing with suppressed scarring. S1P can be a novel therapeutic molecule with anti-scarring effect in surgical, trauma, and chronic wound management.