Insight into the Healing of Chronic Wounds

Chronic wounds may heal with more difficulty, because microRNA may inhibit the ability of a protein that signals the skin cells into the action of healing a wound, according to a recent discovery made by researchers at Ohio State University.

Chandan Sen, professor and vice chair for research in the Department of Surgery and senior author of the study, and his research team created ischemic and non-ischemic wounds on the skin of mice. The researchers then determined the levels of blood flow that were traveling to the wounds, finding that the ischemic wounds were hypoxic. This state led to the presence of the protein hypoxia inducible factor-1a, or HIF-1a in the ischemic wounds, which can turn genes on and off, and, in the case of the study, also appeared to influence the behavior of at least one microRNA, according to the researchers. The team then observed that “the presence of HIF-1a in low-oxygen conditions led to the activation of the miR-210,” and that microRNA lowered levels of the protein E2F3, which is used by the skin to heal wounds.

In an additional step, the research team inserted the experimental drug antagomir—a synthetic molecule that renders microRNAs inactive and that was designed, for this study, to act specifically on miR-210—into the cells. This action lowered the miR-210 levels while raising the E2F3 protein levels, which increased the growth of skin cells significantly. However, “when the miR-210 levels were artificially raised using a molecule that mimics its behavior, the skin cells’ growth was compromised.”

“MicroRNAs are induced only by certain conditions. They have specific profiles in the daily biology of a given organ, but under conditions of an injury, certain microRNAs wake up,” Sen said. “Once it sees hypoxia, miR-210 wakes up, and then it governs what happens with the E2F3 protein after that.”