title: Protective effect of MFG-E8 after cutaneous ischemia-reperfusion injury.
abstract: We recently demonstrated that the secreted glycoprotein and integrin-ligand MFG-E8 promotes cutaneous wound healing by enhancing angiogenesis. Several studies have identified potential roles for MFG-E8 in regulation of ischemia-reperfusion (I/R) injury in the brain, kidney, and liver. Our objective was to assess the role of MFG-E8 in the formation of skin ulcers using a murine model of cutaneous I/R injury-cutaneous pressure ulcers. Cutaneous I/R was performed by trapping the dorsal skin between two magnetic plates for 12 hours, followed by plate removal. Expression of MFG-E8 increased in the dermis during ischemia, and then decreased after reperfusion. Administration of recombinant (r)MFG-E8 in I/R areas at the beginning of reperfusion significantly inhibited the formation of cutaneous pressure ulcers, and the number of CD31(+) vessel and NG2(+) pericytes in wounds were increased in I/R mice treated with rMFG-E8. The number of M1 macrophages and the amount of proinflammatory mediators monocyte chemotactic protein-1,induced nitric oxide synthase, IL-6, tumor necrosis factor-α, and IL-1β in the wound area were reduced by the administration of rMFG-E8. We conclude that MFG-E8 may inhibit the formation of pressure ulcers induced by cutaneous I/R injury by regulating angiogenesis and inflammation. Exogenous application of MFG-E8 might have therapeutic potential for cutaneous I/R injuries, including decubitus ulcers and Raynaud's phenomenon-induced digital ulcers.
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Uchiyama
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Buddhini
authors.initials: B
authors.lastname: Perera
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ogino
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yokoyama
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takeuchi
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishikawa
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan. Electronic address: smotegi@gunma-u.ac.jp.
authors.forename: Sei-Ichiro
authors.initials: SI
authors.lastname: Motegi
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D017209:Apoptosis; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008024:Ligands; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008894:Milk Proteins / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009389:Neovascularization, Pathologic; D009569:Nitric Oxide / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D003668:Pressure Ulcer / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015427:Reperfusion Injury; D012867:Skin / Q000378:metabolism; D012871:Skin Diseases / Q000378:metabolism*; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014945:Wound Healing
chemical_list: D000954:Antigens, Surface; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D008024:Ligands; C098942:MFGE8 protein, human; C490919:Mfge8 protein, mouse; D008894:Milk Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D020797:Receptor, Platelet-Derived Growth Factor beta