Kuo Jennifer H, Cuevas Ileana, Chen Amy, Dunn Ashley, Kuri Mauricio, Boudreau Nancy
Department of Surgery, University of California Davis , Sacramento, California.
Surgical Research Laboratory, University of California San Francisco , San Francisco, California.
Adv Wound Care (New Rochelle). 2014 Oct 1;3(10):605-613. doi: 10.1089/wound.2013.0474.
Homeobox (HOX) transcription factors coordinate gene expression in wound repair and angiogenesis. Previous studies have shown that gene transfer of HoxA3 to wounds of diabetic mice accelerates wound healing, increasing angiogenesis and keratinocyte migration. In this study, we examined whether HoxA3 can also improve angiogenesis, epidermal integrity, and viability of composite skin grafts. To determine the effects of HoxA3 on composite skin grafts, we constructed bilayered composite grafts incorporating fibroblasts engineered to constitutively secrete HoxA3. We then transplanted these composite grafts . The composite grafts produced a stratified epidermal layer after seventeen days in culture and following transplantation , these grafts exhibit normal epidermal differentiation and reduced contraction compared to controls. In addition, HoxA3 grafts showed increased angiogenesis. Quantitative polymerase chain reaction (PCR) analyses of HoxA3 graft tissue reveal an increase in the downstream HoxA3 target genes MMP-14 and uPAR expression, as well as a reduction in CCL-2 and CxCl-12. Expression of secreted HoxA3 in composite grafts represents a comprehensive approach that targets both keratinocytes and endothelial cells to promote epidermal proliferation and angiogenesis. Secreted HoxA3 improves angiogenesis, reduces expression of inflammatory mediators, and prolongs composite skin graft integrity.
同源框（HOX）转录因子在伤口修复和血管生成过程中协调基因表达。先前的研究表明，将HoxA3基因转移至糖尿病小鼠的伤口可加速伤口愈合，增加血管生成和角质形成细胞迁移。在本研究中，我们检测了HoxA3是否也能改善复合皮肤移植物的血管生成、表皮完整性和活力。为了确定HoxA3对复合皮肤移植物的影响，我们构建了包含经基因工程改造可组成性分泌HoxA3的成纤维细胞的双层复合移植物。然后我们移植了这些复合移植物。复合移植物在培养17天后形成了分层的表皮层，移植后，与对照相比，这些移植物表现出正常的表皮分化且收缩减少。此外，HoxA3移植物显示出血管生成增加。对HoxA3移植物组织进行的定量聚合酶链反应（PCR）分析显示，下游HoxA3靶基因MMP - 14和uPAR的表达增加，以及CCL - 2和CxCl - 12的表达减少。复合移植物中分泌型HoxA3的表达代表了一种针对角质形成细胞和内皮细胞以促进表皮增殖和血管生成的综合方法。分泌型HoxA3可改善血管生成，降低炎症介质的表达，并延长复合皮肤移植物的完整性。
