College of Pharmacy, CHA University, 335, Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488 Republic of Korea.
Graduate School of Pharmaceutical Sciences and College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea.
Biomed Pharmacother. 2020 Jan;121:109613. doi: 10.1016/j.biopha.2019.109613. Epub 2019 Nov 7.
Diabetic foot ulcers represent one of the major and rising health issues, as the number of diabetic patients is increasing. MicroRNAs (miRNAs) are among various bioactive molecules under investigation for diabetic wound healing. The prolonged pro-inflammatory phase in diabetic wounds partly attributes to its non-healing nature. Therefore, we hypothesized that miRNA-497, known for its regulation of inflammatory responses, would enhance diabetic wound healing. We screened miRNA candidates, including miRNA-497 in the wounded skin of streptozotocin-induced type 1 diabetic mice. The therapeutic potential of miRNA-497 mimic was studied by intradermal injection around the wound in diabetic mice. In addition, the effects of miRNA-497 on pro-inflammatory cytokines were analyzed in the wound lesion of diabetic mice, and in human dermal fibroblasts cells exposed to high glucose and lipopolysaccharide.We found a significant reduction of miRNA-497 expression in the dermal wounds of the diabetic mice relative to normal mice. Intradermal injection of miRNA-497 around the full-thickness dermal wounds in diabetic mice accelerated wound closure effectively compared to the control miRNA. miRNA-497 treatment in vivo and in vitro decreased representative pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α. Such anti-inflammatory effects of miRNA-497 shed light on its role in accelerating diabetic wound healing. In conclusion, miRNA-497, with its down-regulation activity for pro-inflammatory cytokines, is proposed as a potential therapeutic agent for diabetic wound healing.
糖尿病足溃疡是一个主要且日益严重的健康问题，因为糖尿病患者的数量正在增加。 microRNAs（miRNAs）是正在研究用于糖尿病伤口愈合的各种生物活性分子之一。糖尿病伤口中炎症反应的持续延长部分归因于其不易愈合的性质。因此，我们假设 miRNA-497（已知其可调节炎症反应）会增强糖尿病伤口愈合。我们筛选了 miRNA 候选物，包括链脲佐菌素诱导的 1 型糖尿病小鼠伤口皮肤中的 miRNA-497。通过在糖尿病小鼠的伤口周围皮内注射来研究 miRNA-497 模拟物的治疗潜力。此外，还分析了 miRNA-497 对糖尿病小鼠伤口病变中促炎细胞因子的影响，以及高糖和脂多糖暴露的人真皮成纤维细胞。我们发现糖尿病小鼠真皮伤口中的 miRNA-497 表达明显低于正常小鼠。与对照 miRNA 相比，在糖尿病小鼠全层真皮伤口周围皮内注射 miRNA-497 可有效加速伤口闭合。miRNA-497 在体内和体外的治疗可降低代表性促炎细胞因子，如 IL-1β、IL-6 和 TNF-α。miRNA-497 的这种抗炎作用表明其在加速糖尿病伤口愈合中的作用。总之，miRNA-497 下调促炎细胞因子的活性，可作为糖尿病伤口愈合的潜在治疗剂。
