STANFORD, Calif. Researchers at the Stanford University School of Medicine report that they have identified the molecular pathway through which physical force contributes to scarring in mice.
"Our study exposes one of the fundamental mechanisms by which the mechanical environment can directly increase inflammation, which is strongly implicated in scarring," said Geoffrey Gurtner, MD, professor and associate chair of surgery.
Mice genetically engineered to lack an enzyme that is activated by mechanical force demonstrated less inflammation and fibrosis the formation of excess fibrous connective tissue in their incisions than mice in a control group, the study found. Inflammation and scar formation also were reduced among mice injected with an organic compound, a small molecule called PF-573228, that blocks this enzyme, which helps cells sense changes in the mechanical environment.
While further testing is needed to determine the validity of the findings in humans, the researchers say they hope their work will pave the way for new treatments of fibrotic diseases disorders caused by excess scarring, such as pulmonary fibrosis (the buildup of scar tissue in the lungs) as well as inflammatory diseases, such as rheumatoid arthritis.
The study will be published online Dec. 11 in Nature Medicine. Gurtner is the senior author. The lead author is postdoctoral scholar Victor Wong, MD.
Inflammation, an important part of healing, occurs when white blood cells and the chemicals they release try to kill bacteria and eat up damaged tissue at the site of an injury. However, inflammation is also linked to scarring. Excessive scarring is known as fibrosis. And while there are chemical mechanisms that lead to inflammation, mechanical forces generally have been overlooked as a key stimulator of this biological response and as a possible therapeutic target, the researchers say. An example of such a force would be the pulling on an i
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Stanford University Medical Center