Idlett-Ali Shaquia, Liechty Kenneth W, Xu Junwang
Department of Surgery Laboratory for Fetal and Regenerative Biology, University of Colorado, Denver-Anschutz Medical Campus and Children's Hospital of Colorado, Aurora, Colorado 80045, USA.
J Immunobiol. 2021;6(1). Epub 2021 Feb 1.
Chronic inflammation plays a major role in impaired healing of diabetic wounds. Mounting evidence highlights the role of controlled, sequential polarization of macrophages in producing the appropriate progression through the stages of wound healing: inflammation (pro- inflammatory stage), proliferation and remodeling (regenerative stage). Non-coding RNAs, including microRNAs, maintain critical roles in regulating normal biological processes, such as wound healing; and are being explored as therapeutic targets for modulating dysfunction in disease states. Interestingly, microRNA-21 (miR-21) has a suggested role in the induction of pro-inflammatory and regenerative stages of healing, but clarity remains elusive on the specific mechanisms determining the direction miR-21 shifts wound healing processes. Findings by Liechty et al. in International Journal of Molecular Science indicate an important role of miR-21, in shaping the wound healing cascade by preferentially inducing M1-like (pro-inflammatory) polarization of macrophages in the early phase of diabetic wound healing. Persistent elevation of miR-21 is suggestive of sustained pro-inflammatory drive, and subsequent wound healing impairment, in the skin of diabetic murine models and diabetic human skin. Differences in the expression patterns of miR-21 during diabetic wound healing identifies the potentially critical role of therapeutic timing, for miR-21 based therapies, in driving positive outcomes for patients.
慢性炎症在糖尿病伤口愈合受损中起主要作用。越来越多的证据表明，巨噬细胞的可控、顺序极化在伤口愈合各阶段（炎症期（促炎阶段）、增殖和重塑期（再生阶段））的适当进展中发挥作用。包括微小RNA在内的非编码RNA在调节正常生物过程（如伤口愈合）中发挥关键作用，并且正在作为调节疾病状态下功能障碍的治疗靶点进行探索。有趣的是，微小RNA-21（miR-21）在愈合的促炎和再生阶段的诱导中具有一定作用，但决定miR-21改变伤口愈合过程方向的具体机制仍不清楚。利希蒂等人在《国际分子科学杂志》上的研究结果表明，miR-21在糖尿病伤口愈合早期通过优先诱导巨噬细胞向M1样（促炎）极化来塑造伤口愈合级联反应中起重要作用。在糖尿病小鼠模型和糖尿病患者皮肤中，miR-21的持续升高提示持续的促炎驱动以及随后的伤口愈合受损。糖尿病伤口愈合过程中miR-21表达模式的差异表明，基于miR-21的治疗的治疗时机对于为患者带来积极结果可能具有关键作用。
