title: Low-energy extracorporeal shock wave therapy enhances skin wound healing in diabetic mice: a critical role of endothelial nitric oxide synthase.
abstract: Low-energy extracorporeal shock wave (LE-ESW) treatment has been shown to accelerate wound repair; however, the mechanisms of treatment remain unclear. In the present study, we addressed the role of endothelial nitric oxide synthase (eNOS). A single LE-ESW treatment accelerated the healing of wounds in diabetic mice caused by the injection of streptozotocin. This accelerated healing was accompanied by the increased expression of eNOS and vascular endothelial growth factor (VEGF) and the generation of new vessels at the wound tissues. These results raised the possibility that eNOS may be involved in the beneficial effects of LE-ESW treatment. To address this possibility, we compared the effects of this treatment between mice with a genetic disruption of eNOS knockout (eNOS-KO mice) and wild-type (WT) control mice. Interestingly, the LE-ESW-induced acceleration of wound closure and the increase in VEGF expression and neovascularization was significantly attenuated in eNOS-KO mice compared with WT mice. Considered collectively, these results showed that eNOS was induced at the wound tissues by LE-ESW treatment and played a critical role in the therapeutic effects of this treatment by accelerating the wound healing by promoting VEGF expression and neovascularization.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan. tonosato@med.tohoku.ac.jp
authors.forename: Denso
authors.initials: D
authors.lastname: Hayashi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
authors.forename: Kenta
authors.initials: K
authors.lastname: Ito
authors.forename: Keiko
authors.initials: K
authors.lastname: Ishii
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tanno
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Imai
authors.forename: Emi
authors.initials: E
authors.lastname: Kanno
authors.forename: Ryoko
authors.initials: R
authors.lastname: Maruyama
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tachi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008833:Microcirculation; D018919:Neovascularization, Physiologic; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012883:Skin Ulcer / Q000473:pathology / Q000628:therapy*; D014464:Ultrasonic Therapy / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse