School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, UK.
Dental Research Cell and Biomedical Research Unit (DRC-BRULAC), Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Science (SIMATS), Saveetha University, Chennai, India.
FEBS J. 2022 Sep;289(17):5137-5151. doi: 10.1111/febs.16160. Epub 2021 Aug 26.
The growing pipelines of RNA-based therapies herald new opportunities to deliver better patient outcomes for complex disorders such as chronic nonhealing wounds associated with diabetes. Members of the microRNA (miRNA) family of small noncoding RNAs have emerged as targets for diverse elements of cutaneous wound repair, and both miRNA enhancement with mimics or inhibition with antisense oligonucleotides represent tractable approaches for miRNA-directed wound healing. In this review, we focus on miRNA inhibition strategies to stimulate skin repair given advances in chemical modifications to enhance the performance of antisense miRNA (anti-miRs). We first explore miRNAs whose inhibition in keratinocytes promotes keratinocyte migration, an essential part of re-epithelialisation during wound repair. We then focus on miRNAs that can be targeted for inhibition in endothelial cells to promote neovascularisation for wound healing in the context of diabetic mouse models. The picture that emerges is that direct comparisons of different anti-miRNAs modifications are required to establish the most translationally viable options in the chronic wound environment, that direct comparisons of the impact of inhibition of different miRNAs are needed to quantify and rank their relative efficacies in promoting wound repair, and that a standardised human ex vivo model of the diabetic wound is needed to reduce reliance on mouse models that do not necessarily enhance mechanistic understanding of miRNA-targeted wound healing.
基于 RNA 的治疗方法不断涌现，为治疗慢性难愈性糖尿病相关创面等复杂疾病带来了新的机遇。微小 RNA（miRNA）是一类小型非编码 RNA，其家族成员已成为皮肤创面修复各个方面的治疗靶点，miRNA 增强的模拟物或抑制的反义寡核苷酸都代表着 miRNA 导向创面愈合的可行方法。在这篇综述中，我们重点介绍了 miRNA 抑制策略，以刺激皮肤修复，因为在增强反义 miRNA（anti-miR）的性能方面取得了化学修饰的进展。我们首先探讨了那些在角质细胞中抑制能促进角质细胞迁移的 miRNA，角质细胞迁移是创面修复中再上皮化的重要组成部分。然后，我们关注那些可以在血管内皮细胞中靶向抑制以促进血管新生的 miRNA，以促进糖尿病小鼠模型中的创面愈合。由此可见，在慢性创面环境中，需要直接比较不同 anti-miR 修饰物，以确定最具转化潜力的选择；需要直接比较抑制不同 miRNA 的影响，以量化和排名它们在促进创面修复方面的相对功效；需要一个标准化的人类糖尿病创面体外模型，以减少对不一定能增强 miRNA 靶向创面愈合的机制理解的小鼠模型的依赖。
