Department of Surgery, The Ohio State University Medical Center, Columbus, Ohio 43210, USA.
Microcirculation. 2012 Apr;19(3):224-32. doi: 10.1111/j.1549-8719.2011.00156.x.
Chronic wounds represent a rising health and economic burden to our society. Emerging studies indicate that miRNAs play a key role in regulating several hubs that orchestrate the wound inflammation and angiogenesis processes. Of interest to wound inflammation are the regulatory loops where inflammatory mediators elicited following injury are regulated by miRNAs, as well as regulate miRNA expression. Adequate angiogenesis is a key determinant of success in ischemic wound repair. Hypoxia and cellular redox state are among the key factors that drive wound angiogenesis. We provided first evidence demonstrating that miRNAs regulate cellular redox environment via a NADPH oxidase-dependent mechanism in human microvascular endothelial cells (HMECs). We further demonstrated that hypoxia-sensitive miR-200b is involved in induction of angiogenesis by directly targeting Ets-1 in HMECs. These studies point toward a potential role of miRNA in wound angiogenesis. miRNA-based therapeutics represent one of the major commercial hot spots in today's biotechnology market space. Understanding the significance of miRs in wound inflammation and angiogenesis may help design therapeutic strategies for management of chronic nonhealing wounds.
慢性创面给我们的社会带来了日益增长的健康和经济负担。新兴研究表明,miRNAs 在调控几个调控创面炎症和血管生成过程的关键枢纽方面发挥着关键作用。与创面炎症相关的是调节环路,其中损伤后引发的炎症介质受 miRNAs 调控,而 miRNAs 也调控其表达。适当的血管生成是缺血性创面修复成功的关键决定因素。缺氧和细胞氧化还原状态是驱动创面血管生成的关键因素之一。我们提供了初步证据,证明 miRNAs 通过 NADPH 氧化酶依赖的机制在人微血管内皮细胞 (HMECs) 中调节细胞氧化还原环境。我们进一步证明,缺氧敏感的 miR-200b 通过直接靶向 HMECs 中的 Ets-1 参与诱导血管生成。这些研究表明 miRNA 在创面血管生成中可能具有潜在作用。基于 miRNA 的治疗方法是当今生物技术市场的主要商业热点之一。了解 miRs 在创面炎症和血管生成中的意义可能有助于设计慢性难愈创面管理的治疗策略。