The reason behind why chronic wounds have trouble healing- tiny piece of RNA, called as miR-210, scientists have discovered.
In a new animal study, the Ohio State University researchers discovered that this RNA segment in wounds with limited blood flow lowers the production of a protein that is needed to encourage skin cells to grow and close over the sore.
In a parallel experiment using human skin cells, the researchers silenced the RNA segment with an experimental drug and saw those protein levels rise. The skin cells multiplied as a result.
The findings suggest that targeting this RNA segment with a drug that could be used topically on skin might offer new strategies for treating chronic wounds, which are sometimes fatal and cost the U.S. health-care system an estimated 25 billion dollars annually.
RNA in cells is responsible for using instructions from DNA to make proteins, but as miR-210 has a completely different role.
It is a microRNA, a small segment of RNA that blocks an important protein-building process.
The research involves wounds that are ischemic, that is, they heal very slowly or are in danger of never healing because they lack blood flow and oxygen at the wound site.
These types of wounds affect about 6.5 million patients each year, and are common complications of diabetes, high blood pressure, obesity and other conditions characterized by poor vascular health.
"When blood supply is inadequate, many things are deficient at the wound site, including oxygen. That leads to a condition called hypoxia. We have shown that hypoxia induces miR-210, which actually blocks the ability of the cells to proliferate, a step necessary for the wound-closure process," said Chandan Sen.
After studying the effects of low oxygen on wound healing for years, researchers have now been able to identify the sequence of events connecting low oxygen and the inability of skin cells to grow.
Sen said this is the first publication to suggest microRNAs regulate the healing process in chronic wounds.
Sen and colleagues created ischemic and non-ischemic wounds on mouse skin for comparison.
In ischemic mouse wounds, the researchers observed that the hypoxic, or low-oxygen, conditions led to the presence of a specific type of protein called hypoxia inducible factor-1a, or HIF-1a.
This protein can turn genes on and off and, in this case, appears to influence the behaviour of at least one microRNA as well.
The presence of HIF-1a in low-oxygen conditions led to the activation of the miR-210, and that microRNA in turn lowered levels of the protein needed to kick skin cells into action. This protein is called E2F3.
On the other hand, the non-ischemic wounds on the mice showed abundant levels of the E2F3 protein and healed normally within about seven days.
The research appears in the online early edition of the Proceedings of the National Academy of Sciences.