Broad-Spectrum Inhibition of the CC-Chemokine Class Improves Wound Healing and Wound Angiogenesis.
Broad-Spectrum Inhibition of the CC-Chemokine Class Improves Wound Healing and Wound Angiogenesis.
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DOI：
10.3390/ijms18010155
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发表时间：
2017-01-13
影响因子：
5.6
通讯作者：
Tan J
中科院分区：
文献类型：
--
作者：
Ridiandries A;Bursill C;Tan J
血管生成参与创面愈合的炎症和增殖阶段，将炎性细胞带入创面，为维持新的组织形成提供微血管网络。然而，过度的炎症会导致伤口愈合时间延长和疤痕形成，通常会导致截肢等不利结果。CC趋化因子在促进炎症和炎症驱动的血管生成中起关键作用。因此，抑制CC类趋化因子可能会促进伤口愈合。我们的目的是确定广谱CC-趋化因子抑制剂“35K”是否能促进小鼠体内伤口的愈合。在小鼠伤口愈合模型中，每天向伤口局部添加35K蛋白质或磷酸盐缓冲盐水(PBS，对照)。在创伤修复的早期阶段(伤后4天)和后期阶段(伤后10天和21天)对小鼠队列进行评估。局部应用35K蛋白可抑制创面CC-趋化因子(CCL5、CCL2)的表达，促进早、中期创面血流恢复和创面闭合。此外，在伤口修复的早期阶段，35K促进了新生血管的形成。此外，35K处理的创面显著降低了关键的炎症转录因子NF-κB的p65亚单位的表达，并增强了创面促血管生成和修复的细胞因子转化生长因子β的表达。这些发现表明，广谱的CC-趋化因子抑制可能有利于促进伤口愈合。
Angiogenesis is involved in the inflammation and proliferation stages of wound healing, to bring inflammatory cells to the wound and provide a microvascular network to maintain new tissue formation. An excess of inflammation, however, leads to prolonged wound healing and scar formation, often resulting in unfavourable outcomes such as amputation. CC-chemokines play key roles in the promotion of inflammation and inflammatory-driven angiogenesis. Therefore, inhibition of the CC-chemokine class may improve wound healing. We aimed to determine if the broad-spectrum CC-chemokine inhibitor “35K” could accelerate wound healing in vivo in mice. In a murine wound healing model, 35K protein or phosphate buffered saline (PBS, control) were added topically daily to wounds. Cohorts of mice were assessed in the early stages (four days post-wounding) and in the later stages of wound repair (10 and 21 days post-wounding). Topical application of the 35K protein inhibited CC-chemokine expression (CCL5, CCL2) in wounds and caused enhanced blood flow recovery and wound closure in early-mid stage wounds. In addition, 35K promoted neovascularisation in the early stages of wound repair. Furthermore, 35K treated wounds had significantly lower expression of the p65 subunit of NF-κB, a key inflammatory transcription factor, and augmented wound expression of the pro-angiogenic and pro-repair cytokine TGF-β. These findings show that broad-spectrum CC-chemokine inhibition may be beneficial for the promotion of wound healing.