New clues on tissue scarring in scleroderma

April 18, 2014

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: Cancer drug may also work for scleroderma

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

Related Stories

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, ...

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 ...

Recommended for you

Cellphone data can track infectious diseases

August 20, 2015

Tracking mobile phone data is often associated with privacy issues, but these vast datasets could be the key to understanding how infectious diseases are spread seasonally, according to a study published in the Proceedings ...

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.