miR-191-5p: Key Player in Angiogenesis Regulation in Diabetic Foot Ulcers

A study in the European Journal of Medical Research found thatmiR-191-5p is markedly upregulated in diabetic foot ulcers (DFU) and directly impairs angiogenesis and wound healing by suppressing pro‑angiogenic signaling. Clinically, this molecular axis presents both a potential diagnostic marker and a mechanism-based target to address impaired neovascularization in DFU.

The researchers report roughly a 50% increase in serum miR-191-5p in patients with DFU versus uncomplicated type 2 diabetes, with higher levels correlating with larger ulcer area and elevated inflammatory markers. MicroRNA-mediated suppression of angiogenic factors was associated with reduced wound vascularization and measurable angiogenic deficits—an explanatory mechanism for delayed healing in affected patients.

Clinical samples included 207 participants (105 uncomplicated T2DM, 102 DFU). Comparative qRT‑PCR and Western blot analyses assessed miR‑191‑5p and VEGFA expression. Cellular work used high‑glucose HUVEC models with CCK‑8 proliferation, Transwell migration, and tube‑formation assays plus dual‑luciferase reporter testing. Primary endpoints were miR‑191‑5p expression, VEGFA suppression, and angiogenesis metrics.

Dual‑luciferase reporter assays confirmed direct post‑transcriptional binding of miR‑191‑5p to the VEGFA 3′‑UTR, producing significant suppression of reporter activity in wild‑type constructs but not in mutated binding sites (P < 0.05). VEGFA mRNA and protein abundance were reduced in DFU samples and showed a moderate inverse correlation with miR‑191‑5p levels, supporting a direct regulatory relationship that lowers VEGFA availability and angiogenic signaling in DFU tissue.

In endothelial models under high‑glucose conditions, miR‑191‑5p expression increased while endothelial proliferation, migration, and tube formation declined; targeted downregulation of miR‑191‑5p reversed those deficits. Antagonizing miR‑191‑5p restored VEGFA expression, improved endothelial function and angiogenic readouts, and enhanced experimental wound‑healing metrics—findings that support translational evaluation of miR‑191‑5p inhibition to restore angiogenesis in DFU.