Placenta Growth Factor in Diabetic Wound Healing

• DOI: 10.2353/ajpath.2006.051314
• Publication Date: 2006-12-13T19:54:42Z
• Authors: Francesca Cianfarani; Giovanna Zambruno; Laura Brogelli; Francesco Sera; Pedro Miguel Lacal; Maurizio Pesce; Maurizio C. Capog...; Cristina Maria Fa...; Monica Napolitano; Teresa Odorisio
• Keywords: Transcriptional Activation; Wound Healing; 0303 health sciences; Gene Transfer Techniques; Mice, Transgenic; Genetic Therapy; Fibroblasts; Pregnancy Proteins; Adenoviridae; Diabetes Mellitus, Experimental; 3. Good health; Mice; 03 medical and health sciences; Placenta, growth factor, diabetis, wound healing; Cell Movement; Animals; Humans; Placenta Growth Factor; Skin

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.