Department of Orthodontics and Oral Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Curr Drug Targets. 2010 Dec;11(12):1571-85. doi: 10.2174/1389450111009011571.
Wound healing is an intricate process requiring the concerted action of keratinocytes, fibroblasts, endothelial cells, and macrophages. Here, we review the literature on normal wound healing and the pathological forms of wound healing, such as hypertrophic or excessive scar formation, with special emphasis on the heme-heme oxygenase (HO) system and the versatile effector molecules that are formed after HO-mediated heme degradation. Excessive scar formation following wounding is thought to relate to prolonged oxidative and inflammatory stress in the skin. Evidence is accumulating that the heme-HO system forms a novel and important target in the control of wound healing. Heme-protein derived heme can act as a potent oxidative and inflammatory stress inducer, and excess levels of heme may thus contribute to delayed resolution of oxidative and inflammatory insults in the skin. This emphasizes the need for a timely reduction of the levels of heme. Heme-binding proteins, heme transporters, and the heme degrading protein, HO, form therefore a necessary defense. Deficiencies in these defense proteins or a disturbed redox status, as in diabetic patients, may render individuals more prone to heme-induced deleterious effects. A better understanding of the heme-heme oxygenase system as target during wound healing may result in novel strategies to reduce scar formation.
伤口愈合是一个复杂的过程，需要角质形成细胞、成纤维细胞、内皮细胞和巨噬细胞的协同作用。在这里，我们回顾了正常伤口愈合和病理性伤口愈合的文献，如肥厚性或过度瘢痕形成，并特别强调了血红素-血红素加氧酶（HO）系统以及 HO 介导的血红素降解后形成的多功能效应分子。创伤后过度瘢痕形成被认为与皮肤中氧化和炎症应激的延长有关。越来越多的证据表明，血红素-HO 系统是控制伤口愈合的一个新的重要靶点。血红素蛋白衍生的血红素可以作为一种有效的氧化和炎症应激诱导剂，因此过量的血红素可能导致皮肤中氧化和炎症损伤的延迟缓解。这强调了需要及时降低血红素的水平。血红素结合蛋白、血红素转运蛋白和血红素降解蛋白 HO 因此形成了必要的防御。这些防御蛋白的缺乏或氧化还原状态的紊乱，如在糖尿病患者中，可能使个体更容易受到血红素诱导的有害影响。更好地了解血红素-血红素加氧酶系统作为伤口愈合过程中的靶点，可能会产生减少瘢痕形成的新策略。
