New findings on potential target genes for treating venous ulcers

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Micro-RNA regulates hundreds of genes and plays an important role in skin wound healing. However, limited information about how microRNAs regulate gene expression in human wounds has hampered the identification of potentially useful microRNAs for therapeutic targets, he says. Chuang Liuone of the study’s first authors and a postdoctoral fellow at Department of Medicine, SolnaKarolinska Institutet.

To fill this gap, the research team collected 20 samples of wound tissue from healthy volunteers with leg ulcers and from patients with venous ulcers.

RNA sequencing to compare molecules in wounds

Samples were taken on three different occasions to track the healing process. The researchers then used the RNA sequencing to compare the expression of microRNAs and other molecules called messenger RNAs at the same time in both wound healing and non-healing.

They found that 22 μM RNA and 221 mRNAs were expressed at higher levels in venous wounds than in wound healing wounds, while 10 μM RNA and 203 mRNAs were expressed at lower levels. They also found several microparticles with very high or very low levels in venous ulcer target genes.

Next, the researchers conducted a series of experiments on human skin cells called keratinocytes collected from a different substrate from healthy volunteers and patients with venous ulcers. These experiments confirmed the aberrant expression of many of these microparticles and their genetic targets in wound healing.

Opens the door to future treatment

Finally, the researchers were able to show that elevated expression of three RNA molecules in particular — micro-RNA 34a, micro-RNA-424 and micro-RNA-516 — increased the inflammatory response, as well as slowed new growth. Cells and cell migration needed to help close the wound.