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

doi:10.1371/journal.pone.0005803

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 Citations (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.

Original language	English
Journal	PLoS ONE
Volume	4
Issue number	6
Pages (from-to)	e5803
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0005803
Publication status	Published - 1 Jan 2009
Externally published	Yes

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Grochot-Przeczek, A., Lach, R., Mis, J., Skrzypek, K., Gozdecka, M., Sroczynska, P., Dubiel, M., Rutkowski, A., Kozakowska, M., Zagorska, A., Walczynski, J., Was, H., Kotlinowski, J., Drukala, J., Kurowski, K., Kieda, C., Herault, Y., Dulak, J., & Jozkowicz, A. (2009). Heme oxygenase-1 accelerates cutaneous wound healing in mice. PLoS ONE, 4(6), e5803. https://doi.org/10.1371/journal.pone.0005803

Grochot-Przeczek, A, Lach, R, Mis, J, Skrzypek, K, Gozdecka, M, Sroczynska, P, Dubiel, M, Rutkowski, A, Kozakowska, M, Zagorska, A, Walczynski, J, Was, H, Kotlinowski, J, Drukala, J, Kurowski, K, Kieda, C, Herault, Y, Dulak, J & Jozkowicz, A 2009, 'Heme oxygenase-1 accelerates cutaneous wound healing in mice', PLoS ONE, vol. 4, no. 6, pp. e5803. https://doi.org/10.1371/journal.pone.0005803

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title = "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.",

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

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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 ONE

JF - PLoS ONE

IS - 6

ER -

Heme oxygenase-1 accelerates cutaneous wound healing in mice

Abstract

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