Placenta growth factor in diabetic wound healing: Altered expression and therapeutic potential

Francesca Cianfarani, Giovanna Zambruno, Laura Brogelli, Francesco Sera, Pedro Miguel Lacal, Maurizio Pesce, Maurizio C. Capogrossi, Cristina Maria Failla, Monica Napolitano, Teresa Odorisio

Research output: Contribution to journalArticle

Abstract

Reduced microcirculation and diminished expression of growth factors contribute to wound healing impairment in diabetes. Placenta growth factor (PlGF), 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 PlGF-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 PlGF gene transfer to diabetic wounds exerts therapeutic activity by promoting different aspects of the repair process.

Original languageEnglish
Pages (from-to)1167-1182
Number of pages16
JournalAmerican Journal of Pathology
Volume169
Issue number4
DOIs
Publication statusPublished - Oct 2006

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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