Heme oxygenase-1 accelerates cutaneous wound healing in mice.
Heme oxygenase-1 accelerates cutaneous wound healing in mice.
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DOI：
10.1371/journal.pone.0005803
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发表时间：
2009-06-04
期刊：
影响因子：
3.7
通讯作者：
Jozkowicz A
中科院分区：
文献类型：
--
作者：
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
血红素加氧酶-1 （HO-1）是一种细胞保护、促血管生成和抗炎酶，在损伤组织中被强烈诱导。我们的目的是阐明其在皮肤伤口愈合中的作用。在野生型小鼠中，HO-1在伤后第2天和第3天达到最大表达。锡原卟啉- ix对HO-1的抑制导致伤口愈合迟缓。HO-1缺陷小鼠的愈合也被延迟，HO-1的缺乏可能导致完全抑制再上皮化，形成广泛的皮肤病变，并伴有新生血管受损。在角蛋白14启动子控制下的HO-1转基因小鼠中进行的实验表明，角化细胞中HO-1水平的升高足以促进新生血管的形成，加速伤口的愈合。重要的是，在糖尿病小鼠（db/db）中，HO-1在损伤皮肤中的诱导作用相对较弱且延迟，血管生成和伤口愈合也受到损害。在这些动物中，使用腺病毒载体局部递送HO-1转基因加速了伤口愈合并增加了血管化。总之，HO-1的诱导对于有效的伤口闭合和新生血管是必要的。糖尿病小鼠伤口愈合受损可能与HO-1上调延迟有关，并可通过HO-1基因转移得到改善。
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 2nd and 3rd 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.
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