TY - JOUR
T1 - Heme oxygenase-1 accelerates cutaneous wound healing in mice
AU - Grochot-Przeczek, Anna
AU - Lach, Radoslaw
AU - Mis, Jacek
AU - Skrzypek, Klaudia
AU - Gozdecka, Malgorzata
AU - Sroczynska, Patrycja
AU - Dubiel, Milena
AU - Rutkowski, Andrzej
AU - Kozakowska, Magdalena
AU - Zagorska, Anna
AU - Walczynski, Jacek
AU - Was, Halina
AU - Kotlinowski, Jerzy
AU - Drukala, Justyna
AU - Kurowski, Krzysztof
AU - Kieda, Claudine
AU - Herault, Yann
AU - Dulak, Jozef
AU - Jozkowicz, Alicja
PY - 2009/1/1
Y1 - 2009/1/1
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0005803
DO - 10.1371/journal.pone.0005803
M3 - Journal article
C2 - 19495412
SN - 1932-6203
VL - 4
SP - e5803
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 6
ER -