Improved wound healing by dual inhibition of miR‑146a‑5p and miR‑29a‑3p supports a network action of dysregulated miRNAs in diabetic skin – Published online 03/09/2025

Marija Petkovic, Ermelindo C. Leal, Anja E. Sørensen, Per T. Jørgensen, Jesper T. Wengel, Rosa R. Jersie‑Christensen, Jesper T. Troelsen, Eugenia Carvalho, Louise T. Dalgaard

The management of diabetic foot ulcers remains a significant clinical challenge as there are multiple factors that impede healing, including persistent inflammation, oxidative stress, poor vascularisation and extracellular matrix remodelling, often leading to infection or even amputation. In this issue, Petkovic et al (https://doi.org/10.1007/s00125-025-06522-3) investigate an innovative approach to enhance wound healing by focusing on miRNAs (a conserved non-coding gene family that regulates a wide range of biological processes through complex interactions with target mRNA transcripts, thereby regulating gene expression). Two miRNAs, miR-146a-5p and miR-29a-3p, are overexpressed in diabetic skin, disrupting normal healing. The researchers found that repressing both of these miRNAs simultaneously promotes a more optimal regenerative environment for diabetic wounds compared with targeting a single miRNA. The authors conclude that given the pressing need for new therapeutic approaches to complement current diabetic foot ulcer management, the regenerative potential of multi-miRNA modulation offers a promising avenue for enhancing wound repair under diabetic conditions.

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