Recombinant Myxoma Virus-Derived Immune Modulator M-T7 Accelerates Cutaneous Wound Healing and Improves Tissue Remodeling.

Recombinant Myxoma Virus-Derived Immune Modulator M-T7 Accelerates Cutaneous Wound Healing and Improves Tissue Remodeling.
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DOI:
10.3390/pharmaceutics12111003
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发表时间:
2020-10-22
期刊:
影响因子:
5.4
通讯作者:
Lucas AR
Lucas AR
中科院分区:
医学2区
文献类型:
--
作者:
Yaron JR;Zhang L;Guo Q;Awo EA;Burgin M;Schutz LN;Zhang N;Kilbourne J;Daggett-Vondras J;Lowe KM;Lucas AR

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复杂的皮肤伤口是主要的医疗和经济负担,特别是在糖尿病、感染和老年等合并症的情况下。加速和改善或“微调”愈合过程的新方法,从而提高皮肤伤口愈合和管理的质量,是激烈研究的重点。在这里,我们研究了重组免疫调节蛋白的局部应用,该蛋白抑制趋化因子与糖胺聚糖的相互作用,减少小鼠夹板全层切除伤口模型的损伤或过度炎症反应。M-T7是一种37 kda分泌的病毒衍生糖蛋白,在许多炎症免疫病理动物模型中显示出治疗效果。与单纯生理盐水治疗相比,重组M-T7局部治疗显著加速了伤口愈合。愈合的伤口表现出改善组织重塑的特性,这是由胶原蛋白成熟决定的。M-T7治疗可促进愈合创面创面周围血管生成的速度,使TNF、VEGF和CD31水平升高。M-T7治疗后的免疫细胞反应与CCL2水平的保持、表达精氨酸酶-1的M2巨噬细胞和CD4 T细胞丰度的增加有关。因此,重组M-T7局部治疗促进了伤口愈合的促溶解环境,并有可能成为一种新的皮肤组织修复治疗方法。
Complex dermal wounds represent major medical and financial burdens, especially in the context of comorbidities such as diabetes, infection and advanced age. New approaches to accelerate and improve, or “fine tune” the healing process, so as to improve the quality of cutaneous wound healing and management, are the focus of intense investigation. Here, we investigate the topical application of a recombinant immune modulating protein which inhibits the interactions of chemokines with glycosaminoglycans, reducing damaging or excess inflammation responses in a splinted full-thickness excisional wound model in mice. M-T7 is a 37 kDa-secreted, virus-derived glycoprotein that has demonstrated therapeutic efficacy in numerous animal models of inflammatory immunopathology. Topical treatment with recombinant M-T7 significantly accelerated wound healing when compared to saline treatment alone. Healed wounds exhibited properties of improved tissue remodeling, as determined by collagen maturation. M-T7 treatment accelerated the rate of peri-wound angiogenesis in the healing wounds with increased levels of TNF, VEGF and CD31. The immune cell response after M-T7 treatment was associated with a retention of CCL2 levels, and increased abundances of arginase-1-expressing M2 macrophages and CD4 T cells. Thus, topical treatment with recombinant M-T7 promotes a pro-resolution environment in healing wounds, and has potential as a novel treatment approach for cutaneous tissue repair.
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