A research team at Emory University School of Medicine notes in a new study that they have identified a protein that they suggest puts the brakes on muscle repair after ischemic injury.
According to the study, published recently in Nature Communications, this protein is called CD163. The researchers suggest via studies on mice that removing this protein may help boost muscle repair and recovery of blood flow after ischemic injury (damage caused by restriction of blood flow), according to a news release from Emory Health Sciences.
Per the release, these findings may help lead to potential treatments aimed at enhancing muscle regeneration.
CD163 was known to scientists, mostly as a molecule involved in scavenging excess hemoglobin from the body, but its role in regulating muscle repair was not, notes senior author Aloke Finn, MD, assistant professor of medicine (division of cardiology) at Emory University School of Medicine, in the release.
Mice lacking CD163 showed increased blood flow and muscle repair, compared with controls, after an injury coming from a restriction of blood flow in one leg. Examining the mice lacking CD163, Finn and his colleagues were surprised to find that blood vessels and muscle fibers also grew substantially (roughly 10%) in their uninjured legs, the release explains.
Potentially, researchers could try to achieve the effect of removing CD163 in humans by giving patients an antibody against CD163, but more research is needed to know how this might work. CD163 levels have been found to increase in aging humans in multiple studies, per the release.
Finn and his colleagues found that macrophages, which are a type of white blood cell, appear to release a soluble form of CD163 in response to injury. In the blood, CD163 soaks up and counteracts another protein called TWEAK, which stimulates muscle cells to multiply.
In CD163’s absence, TWEAK can have a greater effect, and can apparently stimulate muscle growth distant from the site of injury. When infused into normal mice, TWEAK does not have any effect on muscle growth, possibly because of circulating CD163, the release continues.
Scientists that study muscle cells have been interested in TWEAK for several years, but some studies have suggested that TWEAK negatively regulates muscle regeneration – the opposite of what Finn’s team observed. To prove that TWEAK was needed for the extra repair seen in mice lacking CD163, the researchers showed that if they injected an antibody against TWEAK, thus removing it from the blood, it eliminated the extra repair activity, the release explains.
“I think our results show a specific mechanism by which muscle regeneration takes place. TWEAK can be a pro-regenerative factor,” Finn says in the release, “but its effects have to be transient and limited.”
TWEAK is thought of as transmitting inflammatory signals because it activates a master regulator of inflammation called NF-kB. While chronic inflammation is bad for muscle growth, in the mice lacking CD163, the signals coming from increased TWEAK are helpful for regeneration, the release notes.
“Ischemic injury is a situation in which TWEAK can stimulate muscle progenitor cells to proliferate,” Finn explains in the release. “But if you have lots of TWEAK around all the time, the muscle cells don’t know when it’s time to differentiate and mature. ”
TWEAK has also been shown to be connected to liver regeneration and stroke. Finn notes in the release that his team is currently investigating CD163’s effects on atherosclerosis.
[Source(s): Emory University School of Medicine, EurekAlert]
