Heme oxygenase-1 accelerates cutaneous wound healing in mice

Anna Grochot-Przeczek, Radoslaw Lach, Jacek Mis, Klaudia Skrzypek, Malgorzata Gozdecka, Patrycja Sroczynska, Milena Dubiel, Andrzej Rutkowski, Magdalena Kozakowska, Anna Zagorska, Jacek Walczynski, Halina Was, Jerzy Kotlinowski, Justyna Drukala, Krzysztof Kurowski, Claudine Kieda, Yann Herault, Jozef Dulak, Alicja Jozkowicz

92 Citationer (Scopus)

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.
OriginalsprogEngelsk
TidsskriftPLoS ONE
Vol/bind4
Udgave nummer6
Sider (fra-til)e5803
ISSN1932-6203
DOI
StatusUdgivet - 1 jan. 2009
Udgivet eksterntJa

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