title: Fibronectin potentiates topical erythropoietin-induced wound repair in diabetic mice.
abstract: Diabetes mellitus disrupts all phases of the wound repair cascade and leads to development of chronic wounds. We previously showed that topical erythropoietin (EPO) can promote wound repair in diabetic rats. Fibronectin (FN) has a critical role throughout the process of wound healing, yet it is deficient in wound tissues of diabetic patients. Therefore, we investigated the effect of topical treatment of both EPO and FN (EPO/FN) on wound repair in diabetic mice. Full-thickness excisional skin wounds in diabetic and nondiabetic mice were treated with a cream containing vehicle, EPO, FN, or EPO/FN. We assessed the rate of wound closure, angiogenesis, apoptosis, and expression of inflammatory cytokines, endothelial nitric oxide synthase (eNOS) and β1-integrin, in the wound tissues. We also investigated the effect of EPO, FN, and EPO/FN on human dermal microvascular endothelial cells and fibroblasts cultured on fibrin-coated plates, or in high glucose concentrations. EPO/FN treatment significantly increased the rate of wound closure and this effect was associated with increased angiogenesis, increased eNOS and β1-integrin expression, and reduced expression of inflammatory cytokines and apoptosis. Our findings show that EPO and FN have an additive effect on wound repair in diabetic mice.
authors.affiliation: The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. www.saher@gmail.com
authors.forename: Saher
authors.initials: S
authors.lastname: Hamed
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Ullmann
authors.forename: Dana
authors.initials: D
authors.lastname: Egozi
authors.forename: Essam
authors.initials: E
authors.lastname: Daod
authors.forename: Elias
authors.initials: E
authors.lastname: Hellou
authors.forename: Manal
authors.initials: M
authors.lastname: Ashkar
authors.forename: Amos
authors.initials: A
authors.lastname: Gilhar
authors.forename: Luc
authors.initials: L
authors.lastname: Teot
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004357:Drug Synergism; D042783:Endothelial Cells / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D005353:Fibronectins / Q000494:pharmacology*; D006909:Hydroxyproline / Q000032:analysis; D019012:Integrin beta1 / Q000032:analysis; D051379:Mice; D008812:Mice, Hairless; D052250:Nitric Oxide Synthase Type III / Q000032:analysis; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D005353:Fibronectins; D019012:Integrin beta1; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D013311:Streptozocin; D052250:Nitric Oxide Synthase Type III; D006909:Hydroxyproline