In people with diabetes, wound healing is slow and complex, which favors the appearance of ulcers that are difficult to heal. A new study, led by the University of Coimbra (UC) and the University of Roskilde (Denmark), shows almost complete healing of these wounds after ten days, using a molecular approach that simultaneously inhibits two microRNAs. This method may pave the way for the development of new therapies to improve wound treatment in people diagnosed with diabetes.

“The aim of the study was to investigate whether blocking two microRNAs — miR-146a-5p and miR-29a-3p, which are small molecules that regulate gene expression and which we found to be increased in the skin of people with diabetes — could improve the healing of these wounds”, explain researchers from the Obesity, Diabetes and Complications research team at the UC Center for Neuroscience and Cell Biology (CNC-UC) and the Centre for Innovative Biomedicine and Biotechnology (CiBB), Ermelindo Leal and Eugénia Carvalho.

According to scientists, the results published in the scientific journal Diabetologia “open up new possibilities for the development of innovative therapies that act directly on miR-146a-5p and miR-29a-3p, with the potential to modulate key processes involved in wound healing, such as inflammation, oxidative stress, the formation of new blood vessels, and the remodeling of the extracellular matrix.”

To achieve these results, researchers tested the effect of microRNA inhibition using molecules designed for this purpose, both in human cells and in mice with type 1 diabetes. Subsequently, the consequences in terms of inflammation, new blood vessel formation, and tissue remodeling were analyzed. In tests with mice, the therapeutic approach significantly reduced wound size in ten days, with changes that led to more resistant and structurally more organized skin.

By identifying the two microRNAs as promising therapeutic targets, the study lays the groundwork for future personalized and more effective approaches to treating chronic wounds, especially in people with diabetes. “These future targets for molecular therapy may have the potential to significantly improve wounds and patient recovery, reducing hospital stays, lowering the risk of amputations, and thus alleviating the associated economic and social burden”, say the UC researchers. They may also “enhance similar strategies applied to other pathologies marked by poor healing or chronic inflammation”, they add.

“This study has great social relevance, especially in a global context where diabetes is a disease that affects millions of people — causing pain, recurrent infections, frequent hospitalizations, and even amputations — and shows a trend of continuous growth”, emphasize Ermelindo Leal and Eugénia Carvalho.

There are around 540 million cases of diabetes worldwide. In Portugal, 1.1 million people suffer from the disease. Diabetic ulcers occur in around 25 % of cases, of which around 70 % result in amputations.

In addition to Roskilde University, scientists from other Danish institutions, the University of Southern Denmark, and Aalborg University participated in the study. Marija Petkovic was also part of the CNC-UC team.

The study was supported by several entities: European Foundation for the Study of Diabetes; Danish Diabetes and Endocrine Academy; National Institute on Aging (United States of America); and Foundation for Science and Technology.

The scientific article Improved wound healing by dual inhibition of miR-146a-5p and miR-29a -3p supports a network action of dysregulated miRNAs in diabetic skin is available here.

Inês Amado da Silva (CNC-UC) with Catarina Ribeiro