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.
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Submitted on : Thursday, July 30, 2009 - 9:58:58 AM
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Anna Grochot-Przeczek, Radoslaw Lach, Jacek Mis, Klaudia Skrzypek, Malgorzata Gozdecka, et al.. Heme oxygenase-1 accelerates cutaneous wound healing in mice.. PLoS ONE, Public Library of Science, 2009, 4 (6), pp.e5803. ⟨10.1371/journal.pone.0005803⟩. ⟨hal-00408274⟩



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