Role of the miR-324-3p/GPX4 regulatory axis in diabetic foot ulcer wound healing
Year: 2026
Type: article
Abstract: Transcriptomic studies have identified miR‑324‑3p as a hub dysregulated miRNA in Diabetic foot ulcer (DFU) lesions, and bioinformatic prediction suggests potential targeting of GPX4, a core regulator of ferroptosis. This study aimed to explore the clinical correlation and intrinsic regulatory mechanism of the miR-324-3p/GPX4 axis in the progression of DFU. A total of 320 human subjects, including 100 healthy controls (HC), 100 patients with uncomplicated T2DM (DM), and 120 patients with DFU, were enrolled in this cross‑sectional study. Serum relative expression of miR‑324‑3p and GPX4 enzymatic activity were measured. Their correlations with routine metabolic/inflammatory clinical markers, Wagner ulcer grade, and 28‑day wound‑healing outcomes were analyzed. Human umbilical vein endothelial cells (HUVECs) treated with high glucose (HG) served as an in‑vitro cellular model of diabetic injury. Clinically, circulating miR‑324‑3p expression increased progressively whereas serum GPX4 enzymatic activity decreased across healthy controls, uncomplicated type 2 diabetic patients and DFU patients. Circulating miR‑324‑3p was positively associated with glycemic and inflammatory markers, advanced Wagner grades, and higher 28‑day non‑healing risk in DFU patients, and showed inverse correlation with serum GPX4 activity. In HUVECs, high‑glucose exposure up‑regulated miR‑324‑3p and suppressed GPX4 expression. Inhibition of miR‑324‑3p restored endothelial proliferation and migration, improved intracellular redox homeostasis, and reduced pro‑inflammatory IL‑6 and TNF‑α secretion; these protective effects were completely abolished following GPX4 knockdown. The miR‑324‑3p/GPX4 axis correlates with diabetic foot ulcer severity. In‑vitro data suggest that this axis may participate in high‑glucose‑mediated endothelial dysfunction via regulating inflammation and ferroptosis‑associated injury. This endothelial‑centered pathway may partially contribute to DFU pathogenesis, although clinical findings remain correlative and require further independent validation.
Language: English
Topic: Wound Healing and Treatments
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,090
OpenAlex ID: W7225820329
FWCI:
Cites:
Cited by:
Related to: