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 by John Varga, MD, John and Nancy Hughes Distinguished Professor of Rheumatology at Northwestern University Feinberg School of Medicine, was recently published in the journal Arthritis & Rheumatism.
"We showed, for the first time, that the Wnt signaling pathway is abnormally activated in scleroderma patients," said Varga, who is also a physician at Northwestern Memorial Hospital. "This is significant for three reasons. First, it gives a better picture of scleroderma and fibrosis in general. Second, it provides a strategy for assessing disease severity, progression, and activity. And third, it opens a door for the design of treatments that aim to block the Wnt pathway and restore its normal controlled activity."
Varga's laboratory collaborated with a pulmonary team at Northwestern, along with teams at Case Western Reserve University and Dartmouth University on the discovery.
Researchers studied skin and lung biopsies from scleroderma patients and found that the Wnt pathway was 'turned on', in contrast to healthy individuals where the pathway was 'turned off.' Varga said this activation may be due to loss of Wnt inhibitors that normally serve as 'brakes' on the pathway to prevent its activation.
The team also examined what the pathway does using fibroblasts and stem cells from healthy people. They found Wnt causes fibroblast activation and blocks the development of fat cells (adipocytes), which directly contribute to scar formation and tissue damage seen in scleroderma.
Scleroderma is a chronic autoimmune disease in which the body's immune system attacks itself. It causes progressive thickening and tightening (fibrosis) of the skin and also can lead to serious internal organ damage and, in some cases, death. Scleroderma affects an estimated 150,000 people in the United States, most frequently young to middle-aged women.
"Scleroderma is a complex and poorly understood disease with no cure," said Varga. "Our findings suggest that treatments targeting the Wnt signaling pathway could lead to an effective treatment."
Varga said Northwestern researchers next plan to conduct multi-center preclinical studies to evaluate treatments that block the Wnt pathway in animal models and measure Wnt activity in additional scleroderma biopsies to see if it can be clinically useful as a biomarker.
Marla Paul | EurekAlert!
How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine
Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy