MicroRNA Mechanisms in Diabetic Wound Healing

Diabetic wounds are characterised by chronic inflammation, impaired angiogenesis and delayed re-epithelialisation. MicroRNAs (miRNAs), short non-coding RNAs of ~22 nucleotides, orchestrate key aspects of the healing cascade by binding to target mRNAs and modulating gene expression post-transcriptionally. In diabetes, dysregulated miRNA profiles contribute to sustained inflammatory signalling, reduced growth factor expression and deranged endothelial and keratinocyte function. Specific miRNAs mediating these effects include pro-inflammatory species that amplify NF-κB signalling, angiostatic miRNAs that suppress VEGF pathways and re-epithelialisation inhibitors that target keratinocyte proliferation and migration. Therapeutic strategies aim to restore homeostasis through local inhibition of pathogenic miRNAs or delivery of miRNA mimics, thereby enhancing growth factor availability, normalising macrophage polarisation and promoting vascular and epidermal repair.

Research from Nature Portfolio

Light-activatable antimiRs have been developed to permit spatially restricted inhibition of pathogenic miRNAs in diabetic wounds. Using a photolabile “caged” antimiR-92a, investigators achieved local derepression of Itga5 and Sirt1, thereby enhancing wound cell proliferation and new vessel formation without systemic off-target effects. This approach mimicked the benefits of systemic antimiR therapy while reducing adverse events in other tissues. In addition, topical inhibition of miR-155 in diabetic ulcers was shown to restore fibroblast growth factor 7 expression, attenuate excessive inflammation and accelerate re-epithelialisation and matrix remodelling. Together, these studies demonstrate that precise miRNA modulation at the wound site can rebalance growth and inflammatory signals to improve healing outcomes.

MicroRNA Mechanisms in Diabetic Wound Healing publication trend

The graph below shows the total number of articles in microrna mechanisms in diabetic wound healing across all publications each year (not limited to Nature Index journals).

Technical terms

MicroRNA (miRNA): Small non-coding RNA molecules (~22 nt) that regulate gene expression by binding to complementary sequences in target mRNAs, leading to translational repression or degradation.

AntimiR: Synthetic oligonucleotides designed to bind and inhibit specific miRNAs, thereby preventing their interaction with target mRNAs.

Exosome: Nano-sized extracellular vesicles secreted by cells, carrying proteins, lipids and RNAs; mediate intercellular communication and can deliver miRNAs to distant cells.

Re-epithelialisation: The process by which keratinocytes proliferate and migrate across the wound bed to restore the epidermal barrier.

Angiogenesis: Formation of new blood vessels from pre-existing vasculature, essential for delivering oxygen and nutrients during wound repair.

References

1. Light-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice. Nature Communications (2017).
2. microRNA-155 inhibition restores Fibroblast Growth Factor 7 expression in diabetic skin and decreases wound inflammation. Scientific Reports (2019).
3. Exosomal miRNA-155-5p from M1-polarized macrophages suppresses angiogenesis by targeting GDF6 to interrupt diabetic wound healing. Molecular Therapy - Nucleic Acids (2023).
4. miR-19a/b and miR-20a Promote Wound Healing by Regulating the Inflammatory Response of Keratinocytes. Journal of Investigative Dermatology (2020).
5. MicroRNA-148b Targets the TGF-β Pathway to Regulate Angiogenesis and Endothelial-to-Mesenchymal Transition during Skin Wound Healing. Molecular Therapy (2018).