Plasma exosomal microRNA profiling in diabetic foot ulcers: inflammatory and proliferative stages—an observational study

Diabetic foot ulcers (DFU) are chronic, hard-to-heal wounds that drive diabetic lower-limb complications and can ultimately lead to amputation. Exosomal microRNAs (miRNAs) are promising regulators of ulcer repair by modulating inflammation, promoting angiogenesis, enhancing collagen deposition, and facilitating epithelial regeneration. This study profiled plasma exosomal miRNAs across DFU stages to clarify healing mechanisms and identify potential therapeutic targets. Whole-blood samples were collected from patients with uncomplicated type 2 diabetes (DM, n = 6) and patients with DFU ( n = 13), including an inflammatory-stage group (DFI, n = 7) and a proliferative-stage group (DFP, n = 6).Plasma exosomes were isolated and characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. Next-generation sequencing was used to compare exosomal miRNA expression between DFU stages and DM, followed by RT-qPCR validation of differentially expressed miRNAs. Bioinformatics analyses were performed to assess involved pathways. By comparing the plasma exosomal miRNA profiles of patients with DM and DFU, we found that hsa-miR-744-5p, hsa-miR-432-5p, and hsa-miR-1307-3p were upregulated, whereas hsa-miR-15b -5p, hsa-miR-15a-5p and hsa-miR-144-3p were downregulated in DFU versus DM. RT-qPCR validation confirmed the consistent upregulation of only hsa-miR-744-5p and hsa-miR-1307-3p. KEGG enrichment analysis revealed that the dysregulated miRNAs were primarily associated with inflammation- and angiogenesis-related pathways. The microRNA profiles of plasma exosomes are associated with healing failure in diabetic foot ulcers, with hsa-miR-744-5p and hsa-miR-1307-3p showing sustained upregulation. This suggests that the inflammation-angiogenesis pathway may be involved, indicating that these plasma exosome miRNAs could serve as potential therapeutic targets for DFU. Registration number ChiCTR2500104621; registration date 19 June 2025.