Heme Oxygenase-1 Accelerates Cutaneous Wound Healing in Mice

被引：112

作者：

Grochot-Przeczek, Anna ^{[1
]}

Lach, Radoslaw ^{[1
]}

Mis, Jacek ^{[1
]}

Skrzypek, Klaudia ^{[1
]}

Gozdecka, Malgorzata ^{[1
]}

Sroczynska, Patrycja ^{[1
]}

Dubiel, Milena ^{[1
]}

Rutkowski, Andrzej ^{[1
]}

Kozakowska, Magdalena ^{[1
]}

Zagorska, Anna ^{[1
]}

Walczynski, Jacek ^{[1
]}

Was, Halina ^{[1
]}

Kotlinowski, Jerzy ^{[1
]}

Drukala, Justyna ^{[2
]}

Kurowski, Krzysztof ^{[3
]}

Kieda, Claudine ^{[4
]}

Herault, Yann ^{[5
]}

Dulak, Jozef ^{[1
]}

Jozkowicz, Alicja ^{[1
]}

机构：

[1] Jagiellonian Univ, Dept Med Biotechnol, Fac Biochem Biophys & Biotechnol, Krakow, Poland

[2] Jagiellonian Univ, Dept Cell Biol, Fac Biochem Biophys & Biotechnol, Krakow, Poland

[3] Adamed Ltd, R&D Div, Pienkow, Poland

[4] CNRS, Ctr Mol Biophys, Orleans, France

[5] CNRS, Ctr Transgen Anim, Orleans, France

来源：

PLOS ONE | 2009年 / 4卷 / 06期

基金：

英国惠康基金;

关键词：

D O I：

10.1371/journal.pone.0005803

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

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