Placenta growth factor in diabetic wound healing - Altered expression and therapeutic potential
Placenta growth factor in diabetic wound healing - Altered expression and therapeutic potential
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DOI：
10.2353/ajpath.2006.051314
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发表时间：
2006-10-01
影响因子：
6
通讯作者：
Odorisio, Teresa
中科院分区：
文献类型：
--
作者：
Cianfarani, Francesca;Zambruno, Giovanna;Odorisio, Teresa
微循环减少和生长因子表达减少导致糖尿病伤口愈合障碍。胎盘生长因子（PlGF）是一种促进病理生理性新血管形成的血管生成介质，在皮肤伤口愈合期间表达，并通过增强血管生成来改善伤口闭合。通过使用链脲佐菌素诱导的糖尿病小鼠，我们在这里证明，PlGF诱导强烈减少糖尿病伤口。与糖尿病野生型同窝出生的小鼠相比，皮肤中过表达PlGF的糖尿病转基因小鼠显示出加速的伤口闭合。此外，与用对照载体处理的伤口相比，用表达人PlGF基因的腺病毒载体（AdCMV.PlGF）处理糖尿病伤口显著加速愈合过程。经治疗的伤口的分析显示PlGF基因转移改善肉芽组织形成、成熟和血管化，以及单核细胞/巨噬细胞局部募集。血小板源性生长因子，成纤维细胞生长因子-2，血管内皮生长因子mRNA水平增加AdCMV. PlGF治疗的伤口，可能增强PIGF介导的作用。最后，PlGF处理刺激培养的真皮成纤维细胞迁移，指出PlGF在加速肉芽组织成熟中的直接作用。总之，我们的数据表明，减少PIGF表达有助于糖尿病伤口愈合受损，PIGF基因转移到糖尿病伤口发挥治疗活性，促进不同方面的修复过程。
Reduced microcirculation and diminished expression of growth factors contribute to wound healing impairment in diabetes. Placenta growth factor (PIGF), an angiogenic mediator promoting pathophysiological neovascularization, is expressed during cutaneous wound healing and improves wound closure by enhancing angiogenesis. By using streptozotocin-induced diabetic mice, we here demonstrate that PlGF induction is strongly reduced in diabetic wounds. Diabetic transgenic mice overexpressing PlGF in the skin displayed accelerated wound closure compared with diabetic wild-type littermates. Moreover, diabetic wound treatment with an adenovirus vector expressing the human PlGF gene (AdCMV.PlGF) significantly accelerated the healing process compared with wounds treated with a control vector. The analysis of treated wounds showed that PlGF gene transfer improved granulation tissue formation, maturation, and vascularization, as well as monocytes/macrophages local recruitment. Platelet-derived growth factor, fibroblast growth factor-2, and vascular endothelial growth factor mRNA levels were increased in AdCMV.PlGF-treated wounds, possibly enhancing PIGF-mediated effects. Finally, PlGF treatment stimulated cultured dermal fibroblast migration, pointing to a direct role of PlGF in accelerating granulation tissue maturation. In conclusion, our data indicate that reduced PlGF expression contributes to impaired wound healing in diabetes and that PIGF gene transfer to diabetic wounds exerts therapeutic activity by promoting different aspects of the repair process.