Researchers have identified three gene-regulating molecules—micro-RNAs—that seem to impair the healing of venous ulcers. They conclude that these findings could lead to new treatments for these difficult-to-manage wounds.
As part of this research, published in eLife, the investigators collected 20 wound tissue samples from healthy volunteers with healing wounds on their legs and patients with venous ulcers. Samples were taken at three time points so that the researchers could track the healing process.
The research team then compared the expression of microRNAs and other signalling molecules—messenger RNAs—in healing and non-healing wounds at the three time periods.
“MicroRNAs regulate hundreds of genes and play a crucial role in skin wound repair,” said co-first author Zhuang Liu, PhD, in a press release. “But a limited amount of information about how microRNAs regulate gene expression in human wounds has hampered the identification of microRNAs that could be useful therapeutic targets.”
Dr. Liu is a postdoctoral researcher at the Department of Medicine, Karolinska Institutet in Solna, Sweden.
The research team discovered that 22 microRNAs and 221 messenger RNAs were expressed at higher levels in venous ulcers than in healing wounds. Another 10 microRNAs and 203 messenger RNAs were expressed at lower levels.
They also found that several microRNAs with elevated or abnormally low levels in patients with venous ulcers target genes that are involved in the condition.
Further experiments in human keratinocytes from healthy volunteers and patients with venous ulcers confirmed the abnormal expression of several of these microRNAs and their gene targets in wound healing.
The researchers demonstrated that three of the microRNAs—microRNA-34a, microRNA-424 and microRNA-516—increased the inflammatory response in wounds but also slowed the growth of new cells and cell migration needed for wound closure.
“Our work opens the door to developing new treatments for venous ulcers that reduce the levels of this microRNA trio to help restore normal wound healing in patients,” said co-first author Letian Zhang, PhD, in the release. “MicroRNA-targeting therapies could be more effective and have fewer side effects in patients than some existing therapies for venous ulcers.” Dr. Zhang is a student at the Department of Medicine at the Karolinska Institutet.
The authors note that documenting the microRNAs at different time points in the healing process is particularly important, since elevated microRNA expression might promote healing at one point in the process and hinder it at another.
As part of their study, the team has created a compendium of their findings available online to other researchers who study the wound-healing process.