Shaquia Idlett-Ali, Kenneth W. Liechty and Junwang Xu*
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.
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