Wise Lyn M, Stuart Gabriella S, Real Nicola C, Fleming Stephen B, Mercer Andrew A
Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Adv Wound Care (New Rochelle). 2018 Aug 1;7(8):283-297. doi: 10.1089/wound.2016.0721.
Vascular endothelial growth factor (VEGF) family members are critical regulators of tissue repair and depending on their distinct pattern of receptor specificity can also promote inflammation and scarring. This study utilized a receptor-selective VEGF to examine the role of VEGF receptor (VEGFR)-2 in scar tissue (ST) formation. Cutaneous skin wounds were created in mice using a 4 mm biopsy punch and then treated until closure with purified VEGF-E derived from orf virus stain NZ-2. Tissue samples were harvested to measure gene expression using quantitative PCR and to observe ST formation through histological examination and changes in cell populations by immunofluorescence. VEGFR-2-activation with VEGF-E increased expression of anti-inflammatory cytokine interleukin (IL)-10 and reduced macrophage infiltration and myofibroblast differentiation in wounded skin compared with controls. VEGF-E treatment also increased microvascular density and improved pericyte coverage of blood vessels in the healing wounds. The ST that formed following treatment with VEGF-E was reduced in size and showed improved collagen structure. The role of VEGFR-2 activation in wound epithelialization and angiogenesis is well established; but its contribution to ST formation is unclear. This study tests the effect of a selective VEGFR-2 activation on ST formation following cutaneous wounding in a murine model. VEGFR-2 stimulation can enhance the quality of skin repair, at least, in part, through the induction of IL-10 expression and dampening of wound inflammation and fibrosis. Therapies that selectively activate VEGFR-2 may therefore be beneficial to treat impaired healing or to prevent excess scarring.
血管内皮生长因子（VEGF）家族成员是组织修复的关键调节因子，并且根据其独特的受体特异性模式，还可促进炎症和瘢痕形成。本研究利用一种受体选择性VEGF来检测VEGF受体（VEGFR）-2在瘢痕组织（ST）形成中的作用。使用4毫米活检打孔器在小鼠身上制造皮肤伤口，然后用源自orf病毒株NZ-2的纯化VEGF-E进行治疗直至伤口闭合。收集组织样本，使用定量PCR测量基因表达，并通过组织学检查观察ST形成，通过免疫荧光观察细胞群体的变化。与对照组相比，用VEGF-E激活VEGFR-2可增加抗炎细胞因子白细胞介素（IL）-10的表达，并减少受伤皮肤中的巨噬细胞浸润和成肌纤维细胞分化。VEGF-E治疗还增加了微血管密度，并改善了愈合伤口中血管的周细胞覆盖。用VEGF-E治疗后形成的ST尺寸减小，胶原结构改善。VEGFR-2激活在伤口上皮化和血管生成中的作用已得到充分证实；但其对ST形成的贡献尚不清楚。本研究在小鼠模型中测试了选择性激活VEGFR-2对皮肤创伤后ST形成的影响。VEGFR-2刺激至少部分地通过诱导IL-10表达以及减轻伤口炎症和纤维化来提高皮肤修复质量。因此，选择性激活VEGFR-2的疗法可能有利于治疗愈合受损或预防过度瘢痕形成。
