Scar findings could lead to new therapies

December 11, 2011, Stanford University Medical Center

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 , which is strongly implicated in ," said Geoffrey Gurtner, MD, professor and associate chair of surgery.

Mice genetically engineered to lack an enzyme that is activated by 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 incision when a patient moves; it's the reason stitches are sometimes needed.

"We just haven't taken the physical environment — the environment of mechanical forces that hold all our cells together — seriously enough as a source of inflammation and fibrosis," Gurtner said.

Previous studies have implicated the enzyme, known as focal adhesion kinase, in cellular responses to force, but whether it played a role in inflammation and scarring remained unclear. When the researchers had it genetically engineered out of mice for the current study, incisions in those mice healed normally but scarring was markedly diminished. Ten days after the mice sustained a skin incision, 48 percent fewer scar-tissue cells had formed around it compared with incisions in a control group, according to the study.

The researchers found that the enzyme appears to modulate protein molecules often used by cells to communicate with one another. In test tube studies, mouse scar tissue missing the enzyme did not respond normally to mechanical stimuli and released far lower levels of inflammatory mediators.

The researchers also tested the effects of the enzyme-inhibiting molecule (PF-573228) on human cells that play a key role in wound healing and found that the molecules that stimulate inflammation were not released.

Tests on humans are needed before researchers can evaluate whether this approach could serve as the basis for a valid therapy. The researchers said they hope their findings can eventually be used to develop treatments for diseases that involve excess scarring throughout the body. "These results suggest that targeted strategies to uncouple mechanical force from inflammation and may prove clinically successful across diverse organ systems," they concluded.

Explore further: Scarred lungs leave trail of beta arrestins

Related Stories

Scarred lungs leave trail of beta arrestins

March 28, 2011
Targeting a family of signaling proteins called beta arrestins may stop the life-threatening scarring and thickening of lungs associated with pulmonary fibrosis, reports a new Science study in mice.

Cancer drug may also work for scleroderma

September 22, 2011
A drug used to treat cancer may also be effective in diseases that cause scarring of the internal organs or skin, such as pulmonary fibrosis or scleroderma.

Skin care: new research into scar-free healing

January 21, 2008
New research from the University of Bristol shows that by suppressing one of the genes that normally switches on in wound cells, wounds can heal faster and reduce scarring. This has major implications not just for wound victims ...

New insights come from tracing cells that irreversibly scar lungs

December 1, 2011
Idiopathic Pulmonary Fibrosis (IPF) is an incurable disease in which the delicate gas exchange region of the lung fills with scar tissue, which interferes with breathing. Now researchers at Duke University Medical Center ...

When healing turns to scarring: Research reveals why it happens and how to stop it

September 18, 2008
For the first time, research from The University of Western Ontario has revealed the mechanisms involved in the origin of scarring or fibrotic diseases, as well as a way to control it. The study, led by Andrew Leask of the ...

Researchers show that fibrosis can be stopped, cured and reversed

December 27, 2007
University of California, San Diego researchers have proven in animal studies that fibrosis in the liver can be not only stopped, but reversed. Their discovery, to be published in PLoS Online on December 26, opens the door ...

Recommended for you

New imaging technique can spot tuberculosis infection in an hour

August 16, 2018
Guided by glowing bacteria, researchers have devised an imaging technique that can diagnose live tuberculosis in an hour and help monitor the efficacy of treatments. That's particularly critical because many TB strains have ...

Research shows it's possible to reverse damage caused by aging cells

August 15, 2018
What's the secret to aging well? University of Minnesota Medical School researchers have answered it- on a cellular level.

This matrix delivers healing stem cells to injured elderly muscles

August 15, 2018
A car accident leaves an aging patient with severe muscle injuries that won't heal. Treatment with muscle stem cells from a donor might restore damaged tissue, but doctors are unable to deliver them effectively. A new method ...

Male tobacco smokers have brain-wide reduction of CB1 receptors

August 15, 2018
Chronic, frequent tobacco smokers have a decreased number of cannabinoid CB1 receptors, the "pot receptor", when compared with non-smokers, reports a study in Biological Psychiatry.

Byproducts of 'junk DNA' implicated in cancer spread

August 14, 2018
The more scientists explore so-called "junk" DNA, the less the label seems to fit.

Doctors may be able to enlist a mysterious enzyme to stop internal bleeding

August 14, 2018
Blood platelets are like the sand bags of the body. Got a cut? Platelets pile in to clog the hole and stop the bleeding.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Argiod
3 / 5 (2) Dec 11, 2011
I have always used arnica extract, applied topically, for scar reduction, and have successfully reduced or removed many heavily keloided scars.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.