Anna Grochot-Przeczek 1 , Radoslaw Lach 1 , Jacek Mis 1 , Klaudia Skrzypek 1 , Malgorzata Gozdecka 1 , Patrycja Sroczynska 1 , Milena Dubiel 1 , Andrzej Rutkowski 1 , Magdalena Kozakowska 1 , Anna Zagorska 1 , Jacek Walczynski 1 , Halina Was 1 , Jerzy Kotlinowski 1 , Justyna Drukala 2 , Krzysztof Kurowski 3 , Claudine Kieda 4 , Yann Herault 5 , Jozef Dulak 1 , * , Alicja Jozkowicz 1 , *
4 June 2009
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.