title: Effects of Remote Ischemic Preconditioning on Heme Oxygenase-1 Expression and Cutaneous Wound Repair.
abstract: Skin wounds may lead to scar formation and impaired functionality. Remote ischemic preconditioning (RIPC) can induce the anti-inflammatory enzyme heme oxygenase-1 (HO-1) and protect against tissue injury. We aim to improve cutaneous wound repair by RIPC treatment via induction of HO-1. RIPC was applied to HO-1-luctransgenic mice and HO-1 promoter activity and mRNA expression in skin and several other organs were determined in real-time. In parallel, RIPC was applied directly or 24h prior to excisional wounding in mice to investigate the early and late protective effects of RIPC on cutaneous wound repair, respectively. HO-1 promoter activity was significantly induced on the dorsal side and locally in the kidneys following RIPC treatment. Next, we investigated the origin of this RIPC-induced HO-1 promoter activity and demonstrated increased mRNA in the ligated muscle, heart and kidneys, but not in the skin. RIPC did not change HO-1 mRNA and protein levels in the wound 7 days after cutaneous injury. Both early and late RIPC did not accelerate wound closure nor affect collagen deposition. RIPC induces HO-1 expression in several organs, but not the skin, and did not improve excisional wound repair, suggesting that the skin is insensitive to RIPC-mediated protection.
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands. niels.cremers@radboudumc.nl.|Department of Rheumatology, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands. niels.cremers@radboudumc.nl.|Radboud Institute for Molecular Life Sciences, Nijmegen 6500HB, The Netherlands. niels.cremers@radboudumc.nl.
authors.forename: Niels A J
authors.initials: NA
authors.lastname: Cremers
authors.affiliation: Central Animal Laboratory, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands. kim.wever@radboudumc.nl.|Radboud Institute for Health Sciences, Nijmegen 6500HB, The Netherlands. kim.wever@radboudumc.nl.
authors.forename: Kimberley E
authors.initials: KE
authors.lastname: Wever
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA. rjwong@stanford.edu.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Wong
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands. rene.vanrheden@radboudumc.nl.|Radboud Institute for Molecular Life Sciences, Nijmegen 6500HB, The Netherlands. rene.vanrheden@radboudumc.nl.
authors.forename: René E M
authors.initials: RE
authors.lastname: van Rheden
authors.affiliation: Department of Rheumatology, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands. eline.vermeij@radboudumc.nl.|Radboud Institute for Molecular Life Sciences, Nijmegen 6500HB, The Netherlands. eline.vermeij@radboudumc.nl.
authors.forename: Eline A
authors.initials: EA
authors.lastname: Vermeij
authors.affiliation: Department of Surgery, University Medical Center Groningen, Groningen 9700RB, The Netherlands. g.m.van.dam@umcg.nl.
authors.forename: Gooitzen M
authors.initials: GM
authors.lastname: van Dam
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands. carine.carels@radboudumc.nl.|Radboud Institute for Molecular Life Sciences, Nijmegen 6500HB, The Netherlands. carine.carels@radboudumc.nl.|Department of Human Genetics, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands. carine.carels@radboudumc.nl.|Department of Oral Health Sciences, Faculty of Medicine, KU Leuven, 3000 Leuven, Belgium. carine.carels@radboudumc.nl.
authors.forename: Carine E
authors.initials: CE
authors.lastname: Carels
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands. dittelundvig@hotmail.com.|Radboud Institute for Molecular Life Sciences, Nijmegen 6500HB, The Netherlands. dittelundvig@hotmail.com.
authors.forename: Ditte M S
authors.initials: DM
authors.lastname: Lundvig
authors.affiliation: Department of Orthodontics and Craniofacial Biology, Radboud University Medical Center, Nijmegen 6500HB, The Netherlands. frank.wagener@radboudumc.nl.|Radboud Institute for Molecular Life Sciences, Nijmegen 6500HB, The Netherlands. frank.wagener@radboudumc.nl.
authors.forename: Frank A D T G
authors.initials: FA
authors.lastname: Wagener
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D019194:Ischemic Preconditioning; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000473:pathology*; D014945:Wound Healing / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D003094:Collagen; D051547:Heme Oxygenase-1
keywords: heme oxygenase-1; remote ischemic preconditioning; tissue injury; wound repair