Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
Institute of Interdisciplinary Research, University of Coimbra, 3004-504 Coimbra, Portugal.
Int J Mol Sci. 2022 Oct 10;23(19):12043. doi: 10.3390/ijms231912043.
A diabetic foot ulcer (DFU) is one of the major complications of diabetes. Wound healing under diabetic conditions is often impaired. This is in part due to the excessive oxidative stress, prolonged inflammation, immune cell dysfunction, delayed re-epithelialization, and decreased angiogenesis present at the wound site. As a result of these multifactorial impaired healing pathways, it has been difficult to develop effective therapeutic strategies for DFU. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in heme degradation generating carbon monoxide (CO), biliverdin (BV) which is converted into bilirubin (BR), and iron. HO-1 is a potent antioxidant. It can act as an anti-inflammatory, proliferative, angiogenic and cytoprotective enzyme. Due to its biological functions, HO-1 plays a very important role in wound healing, in part mediated through the biologically active end products generated by its enzymatic activity, particularly CO, BV, and BR. Therapeutic strategies involving the activation of HO-1, or the topical application of its biologically active end products are important in diabetic wound healing. Therefore, HO-1 is an attractive therapeutic target for DFU treatment. This review will provide an overview and discussion of the importance of HO-1 as a therapeutic target for diabetic wound healing.
糖尿病足溃疡（DFU）是糖尿病的主要并发症之一。在糖尿病条件下，伤口愈合常常受损。这部分是由于过度的氧化应激、炎症持续时间延长、免疫细胞功能障碍、再上皮化延迟和血管生成减少，这些都存在于伤口部位。由于这些多因素的愈合途径受损，因此很难为 DFU 开发有效的治疗策略。血红素加氧酶-1（HO-1）是血红素降解的限速酶，生成一氧化碳（CO）、胆红素（BV），其转化为胆红素（BR）和铁。HO-1 是一种有效的抗氧化剂。它可以作为抗炎、增殖、血管生成和细胞保护酶。由于其生物学功能，HO-1 在伤口愈合中起着非常重要的作用，部分是通过其酶活性产生的生物活性终产物介导的，特别是 CO、BV 和 BR。涉及 HO-1 激活或其生物活性终产物局部应用的治疗策略对糖尿病伤口愈合很重要。因此，HO-1 是治疗 DFU 的一个有吸引力的治疗靶点。这篇综述将概述和讨论 HO-1 作为治疗糖尿病伤口愈合的治疗靶点的重要性。
