Diabetic foot ulcers (DFUs) represent a major complication of diabetes, characterized by impaired wound healing. Tibial transverse transport (TTT), a mechanical intervention technique, has shown clinical efficacy in promoting DFU repair; however, its molecular mechanisms remain largely unclear. This study aimed to explore the role of microRNAs (miRNAs) in the TTT-mediated healing of DFUs and to elucidate their regulatory effects on fibroblast function under hyperglycemic conditions. A diabetic rabbit model with full-thickness foot ulcers was established and treated with TTT. Granulation tissue was harvested for transcriptome sequencing to identify differentially expressed miRNAs. Key candidates (miR-182-5p, miR-150-5p, miR-205-5p) were validated by RT-qPCR. In vitro experiments were conducted on fibroblasts cultured in high-glucose conditions, including gain-of-function assays to assess the impact of miR-182-5p on cell proliferation, migration, and expression of HIF-1α and VEGF. TTT significantly altered the miRNA expression profile in DFU granulation tissue, with miR-182-5p being the most upregulated. Functional studies revealed that miR-182-5p overexpression restored proliferation and migration of high-glucose-exposed fibroblasts, while enhancing HIF-1α/VEGF pathway activity. miR-150-5p and miR-205-5p were also elevated by TTT and may contribute to wound repair via PI3K/Akt activation and VEGFA modulation, respectively. These effects align with findings from recent high-impact studies. TTT promotes DFU healing not only through biomechanical stimulation but also via reprogramming of miRNA-mediated molecular pathways. miR-182-5p, in particular, plays a pivotal role in regulating fibroblast activity and angiogenic signaling, representing a promising target for adjunctive molecular therapies. This study provides novel mechanistic insight into TTT and supports its integration with miRNA-based strategies for enhanced DFU treatment.
Xie et al. (2026) studied this question.