New clues on tissue scarring in scleroderma

April 18, 2014, Northwestern University

A discovery by Northwestern Medicine scientists could lead to potential new treatments for breaking the cycle of tissue scarring in people with scleroderma.

Fibrosis, or scarring, is a hallmark of the disease, and progressive tightening of the skin and lungs can lead to serious organ damage and, in some cases, death.

The concept for new therapeutic options centers on findings made by Swati Bhattacharyya, PhD, research assistant professor in Medicine-Rheumatology, who identified the role that a specific protein plays in promoting fibrosis.

"Our results show how a damage-associated protein called fibronectin (FnEDA) might trigger immune responses that convert normal tissue repair into chronic fibrosis in people with ," Bhattacharyya said. "We also found that FnEDA, which is undetectable in healthy adults, was markedly increased in the skin biopsies of patients with scleroderma."

The study was published April 16 in Science Translational Medicine.

Scleroderma remains a disease with high mortality and no effective treatment. The factors responsible for fibrosis in scleroderma are largely unknown. Working with John Varga, MD, John and Nancy Hughes Distinguished Professor of Rheumatology and director of the Northwestern Scleroderma Program, Bhattacharyya and colleagues previously showed that innate immunity is persistently activated in scleroderma patients.

To investigate the connection between immunity and fibrosis in scleroderma, the scientists looked at skin biopsies of scleroderma patients to identify factors responsible for persistent scarring. They discovered that FnEDA was highly elevated.

To test the theory that FnEDA was needed for the scarring to occur, Bhattacharyya used a genetically engineered mouse lacking the protein and discovered these mice did not develop skin fibrosis.

On a cellular level, FnEDA triggered an immune response in cells, leading to fibrosis. Moreover a small molecule which specifically blocks the cellular immune response triggered by FnEDA was able to prevent in mice.

While the current study focused on scleroderma, the mechanisms uncovered might also underlie more common forms of fibrosis, such as and liver cirrhosis.

"This pioneering study using state of the art experimental approaches is the first to identify an innate immune pathway for scleroderma ," Dr. Varga said. "We expect that the results will shift our thinking about the disease, and hopefully open new avenues for its treatment."

"We have raised the possibility for developing novel therapeutic approaches," Bhattacharyya said. "We are also developing novel small molecules to selectively block the receptor for FnEDA as a potential anti-fibrotic therapy in humans."

Explore further: Researchers implicate well-known protein in fibrosis

More information: "FibronectinEDA Promotes Chronic Cutaneous Fibrosis Through Toll-like Receptor Signaling," by S. Bhattacharyya et al . Science Translational Medicine, 2014

Related Stories

Researchers implicate well-known protein in fibrosis

November 20, 2012
An international multi-disciplinary research team led by Northwestern Medicine scientists has uncovered a new role for the protein toll-like receptor 4 (TLR4) in the development of tissue fibrosis, or scarring.

Flipping the switch on scleroderma

April 4, 2014
Scleroderma is a rare and often fatal disease, causing the thickening of tissue, that currently lacks a cure and any effective treatments. A group of researchers, including a Michigan State University professor, is looking ...

New genetic path for scleroderma: Patient biopsies reveal potential new target for therapy

March 19, 2012
A genetic pathway previously known for its role in embryonic development and cancer has been identified as a target for systemic sclerosis, or scleroderma, therapy. The finding, discovered by a cross-disciplinary team led ...

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.

Northwestern to explore personalized medicine for scleroderma

December 2, 2011
Northwestern Medicine researchers have received two five-year grants totaling $953,000 from the National Institutes of Health's (NIH) National Institute of Arthritis and Musculoskeletal and Skin Diseases to study scleroderma, ...

Recommended for you

A new theory on reducing cardiovascular disease risk in binge drinkers

January 23, 2018
A new study shows that binge drinkers have increased levels of a biomarker molecule—microRNA-21—that may contribute to poor vascular function.

Flu infection study increases understanding of natural immunity

January 23, 2018
People with higher levels of antibodies against the stem portion of the influenza virus hemagglutinin (HA) protein have less viral shedding when they get the flu, but do not have fewer or less severe signs of illness, according ...

New long-acting approach for malaria therapy developed

January 22, 2018
A new study, published in Nature Communications, conducted by the University of Liverpool and the Johns Hopkins University School of Medicine highlights a new 'long acting' medicine for the prevention of malaria.

Virus shown to be likely cause of mystery polio-like illness

January 22, 2018
A major review by UNSW researchers has identified strong evidence that a virus called Enterovirus D68 is the cause of a mystery polio-like illness that has paralysed children in the US, Canada and Europe.

Creation of synthetic horsepox virus could lead to more effective smallpox vaccine

January 19, 2018
UAlberta researchers created a new synthetic virus that could lead to the development of a more effective vaccine against smallpox. The discovery demonstrates how techniques based on the use of synthetic DNA can be used to ...

Study ends debate over role of steroids in treating septic shock

January 19, 2018
The results from the largest ever study of septic shock could improve treatment for critically ill patients and save health systems worldwide hundreds of millions of dollars each year.

0 comments

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.