title: Heme oxygenase-1 accelerates cutaneous wound healing in mice.
abstract: Heme oxygenase-1 (HO-1), a cytoprotective, pro-angiogenic and anti-inflammatory enzyme, is strongly induced in injured tissues. Our aim was to clarify its role in cutaneous wound healing. In wild type mice, maximal expression of HO-1 in the skin was observed on the 2(nd) and 3(rd) days after wounding. Inhibition of HO-1 by tin protoporphyrin-IX resulted in retardation of wound closure. Healing was also delayed in HO-1 deficient mice, where lack of HO-1 could lead to complete suppression of reepithelialization and to formation of extensive skin lesions, accompanied by impaired neovascularization. Experiments performed in transgenic mice bearing HO-1 under control of keratin 14 promoter showed that increased level of HO-1 in keratinocytes is enough to improve the neovascularization and hasten the closure of wounds. Importantly, induction of HO-1 in wounded skin was relatively weak and delayed in diabetic (db/db) mice, in which also angiogenesis and wound closure were impaired. In such animals local delivery of HO-1 transgene using adenoviral vectors accelerated the wound healing and increased the vascularization. In summary, induction of HO-1 is necessary for efficient wound closure and neovascularization. Impaired wound healing in diabetic mice may be associated with delayed HO-1 upregulation and can be improved by HO-1 gene transfer.
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Grochot-Przeczek
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Lach
authors.forename: Jacek
authors.initials: J
authors.lastname: Mis
authors.forename: Klaudia
authors.initials: K
authors.lastname: Skrzypek
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Gozdecka
authors.forename: Patrycja
authors.initials: P
authors.lastname: Sroczynska
authors.forename: Milena
authors.initials: M
authors.lastname: Dubiel
authors.forename: Andrzej
authors.initials: A
authors.lastname: Rutkowski
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kozakowska
authors.forename: Anna
authors.initials: A
authors.lastname: Zagorska
authors.forename: Jacek
authors.initials: J
authors.lastname: Walczynski
authors.forename: Halina
authors.initials: H
authors.lastname: Was
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kotlinowski
authors.forename: Justyna
authors.initials: J
authors.lastname: Drukala
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kurowski
authors.forename: Claudine
authors.initials: C
authors.lastname: Kieda
authors.forename: Yann
authors.initials: Y
authors.lastname: Herault
authors.forename: Jozef
authors.initials: J
authors.lastname: Dulak
authors.forename: Alicja
authors.initials: A
authors.lastname: Jozkowicz
mesh_terms: D000256:Adenoviridae; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D018014:Gene Transfer Techniques; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D007633:Keratins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D019076:Transgenes; D014945:Wound Healing
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D007633:Keratins; D051547:Heme Oxygenase-1