Heme oxygenase-1 accelerates cutaneous wound healing in mice.
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.
Grochot-Przeczek
Anna
A
Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Lach
Radoslaw
R
Mis
Jacek
J
Skrzypek
Klaudia
K
Gozdecka
Malgorzata
M
Sroczynska
Patrycja
P
Dubiel
Milena
M
Rutkowski
Andrzej
A
Kozakowska
Magdalena
M
Zagorska
Anna
A
Walczynski
Jacek
J
Was
Halina
H
Kotlinowski
Jerzy
J
Drukala
Justyna
J
Kurowski
Krzysztof
K
Kieda
Claudine
C
Herault
Yann
Y
Dulak
Jozef
J
Jozkowicz
Alicja
A
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
D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D007633:Keratins; D051547:Heme Oxygenase-1