New clues on tissue scarring in scleroderma

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."

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

add to favorites email to friend print save as pdf

Related Stories

Researchers implicate well-known protein in fibrosis

Nov 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

Apr 04, 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, ...

Cancer drug may also work for scleroderma

Sep 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.

New Target Identified for Scleroderma Therapy

Jun 14, 2010

(PhysOrg.com) -- Investigators at Northwestern University Feinberg School of Medicine have identified the molecule Egr-1 (early growth response factor 1) as a new therapy target for scleroderma, an autoimmune disease for ...

Recommended for you

New treatment fights common infant virus

6 hours ago

Researchers at Le Bonheur Children's Hospital and the University of Tennessee Health Science Center announced results of a clinical trial of a new drug shown to safely reduce the viral load and clinical illness of healthy ...

User comments