Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School, Tokyo 113-8603, Japan.
Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and Massey Cancer Center, Richmond, VA 23298-0011, USA.
Int J Mol Sci. 2019 Jul 10;20(14):3381. doi: 10.3390/ijms20143381.
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)-β1 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.
伤口愈合始于招募分泌与伤口相关因子的炎症细胞。接下来是成纤维细胞的激活和组织构建。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合成酶鞘氨醇激酶-1（SphK1）的表达来研究 S1P 在皮肤伤口愈合中的作用。使用了小鼠切开伤口夹板模型。SphK1 在小鼠伤口中高度表达，SphK1 小鼠表现出延迟的伤口闭合，同时血管生成和炎症细胞募集减少。纳米颗粒介导的局部 SphK1 过表达加速了伤口闭合，与增加的血管生成、炎症细胞募集和各种伤口相关因子相关。SphK1 的过表达也导致了较少的疤痕形成，转化生长因子（TGF）-β1 和 S1P 受体-2（S1PR2）信号之间的相互作用可能起着关键作用。总之，SphK1 发挥了重要作用，增强了免疫力，并通过抑制疤痕形成促进早期伤口愈合。S1P 可以成为一种新型的治疗分子，具有在手术、创伤和慢性伤口管理中抗疤痕形成的作用。
