Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
Int Wound J. 2023 Feb;20(2):467-483. doi: 10.1111/iwj.13895. Epub 2022 Jul 15.
To investigate the relationship between small noncoding microRNA-103 (miR-103) and wound healing of diabetic foot ulcers (DFU) and the underlying molecular mechanism, forty type 2 diabetes mellitus with DFU (DFU group), and 20 patients with a chronic skin ulcer of lower limbs and normal glucose tolerance (SUC group) were included. Quantitative real-time PCR method was used to determine miR-103 expression levels in the wound margin tissue of subjects, and to analyse the relationship between the expression of miR-103 and DFU wound healing. In vitro experiments were also performed to understand the effect of miR-103 on the high glucose-induced injury of normal human dermal fibroblasts (NHDFs) cells. The results showed that the miR-103 expression level in the DFU group was significantly higher than that in the SUC group [5.81 (2.25-9.36) vs 2.08 (1.15-5.72)] (P < 0.05). The expression level of miR-103 in the wound margin tissue of DFU was negatively correlated with the healing rate of foot ulcers after four weeks (P = 0.037). In vitro experiments revealed that miR-103 could inhibit the proliferation and migration of NHDF cells and promote the apoptosis of NHDF cells by targeted regulation of regulator of calcineurin 1 (RCAN1) gene expression in a high glucose environment. Down-regulation of miR-103 could alleviate high glucose-induced NHDF cell injury by promoting RCAN1 expression. Therefore, the increased expression of miR-103 is involved in the functional damage of NHDF cells induced by high-glucose conditions, which is related to poor wound healing of DFU. These research findings will provide potential targets for the diagnosis and treatment of chronic skin wounds in diabetes.
为了探究小非编码 microRNA-103（miR-103）与糖尿病足溃疡（DFU）愈合的关系及其潜在的分子机制，纳入 40 例 2 型糖尿病合并 DFU（DFU 组）和 20 例下肢慢性皮肤溃疡且血糖正常的患者（SUC 组）。采用实时定量 PCR 法检测受试者创面边缘组织中 miR-103 的表达水平，并分析 miR-103 的表达与 DFU 创面愈合的关系。还进行了体外实验，以了解 miR-103 对高糖诱导的正常人皮肤成纤维细胞（NHDFs）损伤的影响。结果显示，DFU 组 miR-103 的表达水平明显高于 SUC 组[5.81（2.25-9.36）比 2.08（1.15-5.72）]（P<0.05）。DFU 创面边缘组织中 miR-103 的表达水平与四周后足部溃疡的愈合率呈负相关（P=0.037）。体外实验表明，miR-103 可通过靶向调控钙调神经磷酸酶 1（RCAN1）基因的表达，抑制高糖环境下 NHDF 细胞的增殖和迁移，促进 NHDF 细胞的凋亡。下调 miR-103 可通过促进 RCAN1 表达缓解高糖诱导的 NHDF 细胞损伤。因此，miR-103 的高表达参与了高糖条件下 NHDF 细胞功能损伤，与 DFU 创面愈合不良有关。这些研究结果将为糖尿病慢性皮肤伤口的诊断和治疗提供潜在的靶点。
