Navigation Links
Researchers implicate well-known protein in fibrosis
Date:11/20/2012

Chicago --- 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.

This finding, recently reported in the American Journal of Pathology, has implications for the treatment of scleroderma, a condition for which there currently is no effective treatment.

TLR4 was previously implicated in inflammation, but its role in tissue fibrosis was unknown. Fibrosis is a hallmark of scleroderma and contributes to a range of common diseases including pulmonary fibrosis, kidney fibrosis, liver cirrhosis and radiation-induced scarring.

"We found that when the gene for TLR4 was mutated in mice, the mice became resistant to experimental scleroderma," said the study's first author Swati Bhattacharyya, research assistant professor of rheumatology at Northwestern University Feinberg School of Medicine. "Moreover, scleroderma patients showed abnormal TLR4 levels in fibrotic skin and lung tissue. This tells us we have found a therapeutic target."

Scleroderma is a chronic autoimmune disease which causes progressive tightening of the skin and can lead to serious internal organ damage and, in some cases, death. Scleroderma affects an estimated 300,000 people in the U.S., most frequently young-to-middle-aged women. Its cause and pathogenesis are unknown.

"The Northwestern research team continues to make fundamental discoveries that enhance our scientific understanding of scleroderma," said co-author John Varga, M.D., the John and Nancy Hughes Distinguished Professor of Rheumatology and professor of dermatology at Feinberg. "Careful dissection of the role of individual proteins in this disease enables us to make real progress toward novel treatments."

Researchers from Northwestern, Boston University, the University of Pittsburgh and the University Medical Center Nijmegen, Netherlands contributed to the study, which relied on tissue samples from human scleroderma patients and mouse models.

Agents that block TLR4 are already being developed for inflammation and sepsis in humans. Effective TLR4 inhibitor drugs may blunt and even possibly reverse the fibrosis in scleroderma, says Bhattacharyya. However, earlier attempts to develop therapeutics that block TLR4 have met with failure due to toxicity.

"These results, while significant, are preliminary. We now know that TLR4 plays a role in scleroderma, but much research remains to be done to develop safe and effective drugs to inhibit this pathway," she says.

The investigators are currently studying additional mouse models to better understand the role of TLR4 in fibrosis and are developing novel small molecules to selectively block TLR4 as a potential therapy.


'/>"/>
Contact: Marla Paul
marla-paul@northwestern.edu
312-503-8928
Northwestern University
Source:Eurekalert

Related medicine news :

1. Researchers build synthetic membrane channels out of DNA
2. JTCC researchers play important role in groundbreaking study that may change transplant practices
3. Researchers use computer simulations to find true cost of HIV screenings
4. Sleeping Pill Linked to Hospital Falls, Researchers Say
5. Daycare has many benefits for children, but researchers find mysterious link with overweight
6. Researchers outline effective strategies to prevent teen depression and suicide
7. Researchers report potential new treatment to stop Alzheimers disease
8. Feinstein Institute researchers discover plant derivative
9. Sociology, economics researchers receive grant to study development across the human lifespan
10. Genital Injuries Common But Preventable, Researchers Say
11. Researchers identify impact of rheumatoid arthritis and lupus on joint replacement surgery outcomes
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... As health professionals work ... as “patient engagement.” The patient is doing more than filling out a survey; in ... “There is an increasing emphasis in health care and research on the importance of ...
(Date:10/13/2017)... , ... October 13, 2017 , ... PurhealthRX , ... Oil utilizing Purzorb™ technology. Applying the Purzorb™process to full spectrum CBD oil will revolutionize ... providing a CBD form that can be easily incorporated into liquid products, while reducing ...
(Date:10/13/2017)... Calif. (PRWEB) , ... October 13, 2017 , ... Many ... dementia. However, many long-term care insurance companies have a waiver for care if the ... 90-day elimination period, when the family pays for care, is often waived, so the ...
(Date:10/13/2017)... ... October 13, 2017 , ... Yisrayl Hawkins, Pastor and Overseer at ... of the most popular and least understood books in the Holy Scriptures, Revelation. The ... that have baffled scholars for centuries. Many have tossed it off as mere rubbish, ...
(Date:10/13/2017)... (PRWEB) , ... October 13, 2017 , ... “America On ... Christian identity. “America On The Brink” is the creation of published author, William ... several great-grandchildren. As a WWII veteran, he spent thirty years in the Navy. ...
Breaking Medicine News(10 mins):
(Date:9/22/2017)... -- AVACEN Medical (AVACEN) announced that its CE-Marked AVACEN ... with the widespread pain associated with fibromyalgia in the ... Essex, England commented, "I had difficulty ... sleep at all, tremendous pain, with every movement sending ... AVACEN 100] enough, how this has and is helping ...
(Date:9/19/2017)... , Sept. 19, 2017   ZirMed Inc ., ... analytics, today announced that it has been ranked #1 by ... Black Book™ Rankings 2017 User Survey. ZirMed was recognized ... for large hospitals and medical centers over 200 beds and ... Book,s healthcare technology user survey history. ...
(Date:9/18/2017)... Sept. 18, 2017 EpiVax, Inc. ... bioinformatics and immune engineering, today announced a ... A (H7N9) vaccine. ... seasonal influenza and presents a challenge for ... exposure to be effective. Using state-of-the-art bioinformatics and ...
Breaking Medicine Technology: