Sericultural and Apicultural Division, National Institute of Agricultural Science, RDA, Wanju, 55365, Republic of Korea.
Department of Oral Biochemistry, College of Dentistry, Gangneung-Wonju National University, Gangneung, 28644, Republic of Korea.
Sci Rep. 2019 Mar 5;9(1):3448. doi: 10.1038/s41598-019-40027-5.
Angiogenesis plays an important role in active inflammation and wound healing. Our results showed that silk sericin and 4-hexylresorcinol (4HR) increased vascular endothelial growth factor (VEGF) expression in a dose-dependent manner in RAW264.7 cells. Unlike 4HR, silk sericin increased the expression of hypoxia inducible factor-1α (HIF-1α) and HIF-2α. Pretreatment with an HIF inhibitor decreased the sericin-induced increase in VEGF expression. However, the HIF inhibitor did not affect the 4HR-induced increase in VEGF expression. An inhibitor of matrix metalloproteinase (MMP) declined the 4HR-induced increase in VEGF expression. Silk sericin increased production of reactive oxygen species (ROS), whereas 4HR decreased ROS. M1 markers were increased by silk sericin treatment, and M2 markers were increased by 4HR treatment. VEGF and angiogenin expression were higher in rats treated with a 4HR-incorporated silk mat than in rats treated with a silk mat alone. In conclusion, silk sericin and 4HR increased VEGF expression in RAW264.7 cells via HIF-mediated and MMP-mediated pathways, respectively. Silk sericin exerted like pro-oxidant effects and 4HR exerted anti-oxidant effects. Rats treated with a 4HR-incorporated silk mat showed higher levels of VEGF and angiogenin than those treated with a silk mat alone.
血管生成在活跃的炎症和伤口愈合中起着重要作用。我们的结果表明，丝胶和 4-己基间苯二酚（4HR）在 RAW264.7 细胞中以剂量依赖性方式增加血管内皮生长因子（VEGF）的表达。与 4HR 不同，丝胶增加了缺氧诱导因子-1α（HIF-1α）和 HIF-2α的表达。HIF 抑制剂预处理降低了丝胶诱导的 VEGF 表达增加。然而，HIF 抑制剂不影响 4HR 诱导的 VEGF 表达增加。基质金属蛋白酶（MMP）抑制剂降低了 4HR 诱导的 VEGF 表达增加。丝胶增加了活性氧（ROS）的产生，而 4HR 减少了 ROS。丝胶处理增加了 M1 标志物的表达，4HR 处理增加了 M2 标志物的表达。与单独用丝垫治疗的大鼠相比，用 4HR 掺入的丝垫治疗的大鼠的 VEGF 和血管生成素表达更高。总之，丝胶和 4HR 通过 HIF 介导和 MMP 介导的途径分别增加 RAW264.7 细胞中的 VEGF 表达。丝胶表现出类促氧化剂作用，而 4HR 表现出抗氧化作用。用 4HR 掺入的丝垫治疗的大鼠的 VEGF 和血管生成素水平高于单独用丝垫治疗的大鼠。
