Featured Research

from universities, journals, and other organizations

Causes found for stiff skin conditions

Date:
March 20, 2010
Source:
Johns Hopkins Medical Institutions
Summary:
By studying the genetics of a rare inherited disorder called stiff skin syndrome, researchers have learned more about scleroderma, a condition affecting about one in 5,000 people that leads to hardening of the skin as well as other debilitating and often life-threatening problems. The findings, which appear this week in Science Translational Medicine, open doors to testing new treatments.

By studying the genetics of a rare inherited disorder called stiff skin syndrome, researchers at the Johns Hopkins University School of Medicine have learned more about scleroderma, a condition affecting about one in 5,000 people that leads to hardening of the skin as well as other debilitating and often life-threatening problems. The findings, which appear in Science Translational Medicine, open doors to testing new treatments.

"Scleroderma is a common and often devastating condition yet its cause remains mysterious. My greatest hope is that this work will facilitate the development of new and better treatments," says Harry C. Dietz, M.D., the Victor A. McKusick Professor of Genetics and director of the Johns Hopkins William S. Smilow Center for Marfan Syndrome Research.

Also known as systemic sclerosis, scleroderma generally affects previously healthy young adults, causing scarring of skin and internal organs that can lead to heart and lung failure. "Most often individuals with scleroderma do not have other affected family members, precluding use of genetic techniques to map the underlying genes. Instead we turned to a rare but inherited form of isolated skin fibrosis called stiff skin syndrome, hoping to gain a foothold regarding cellular mechanisms that might prove relevant to both conditions," says Dietz.

A number of clues led Dietz and his team to strongly suspect a role for the connective tissue protein fibrillin-1 in these skin conditions. First, excess collagen is a hallmark feature of both stiff skin syndrome and scleroderma. While studying Marfan syndrome, a condition caused by a deficiency of fibrillin-1, the researchers discovered that fibrillin-1 regulates the activity of TGFbeta, a molecule that induces cells to make more collagen. Second, other researchers have shown that duplication of a segment within the fibrillin-1 gene is associated with skin fibrosis in mice. And third, Dietz treated a patient at Johns Hopkins who had both stiff skin syndrome and eye problems associated with Marfan syndrome. "This seemed too much of a coincidence," he says.

So Dietz's team examined patients with stiff skin syndrome and found them to have excessive amounts of fibrillin-1 in the skin. The researchers then sequenced the fibrillin-1 gene in these same patients and found all the stiff skin syndrome mutations clustered in a single region of the fibrillin-1 protein known to interact with neighboring cells. Further examination showed that these mutations prevent fibrillin-1 from interacting with neighboring cells and lead to increased amounts and activity of TGFbeta, which causes excessive collagen outside cells.

The researchers then examined biopsies from patients with scleroderma and found all of the abnormalities seen in stiff skin syndrome. "It appears that fibriillin-1 helps to inform cells about the quality of their surroundings and also provides a mechanism -- by concentrating TGFbeta -- to induce extra cellular matrix production if the cell senses a deficiency," says Dietz. "A breakdown in signaling coupled with excessive fibrillin-1 and TGFbeta leads to a perfect storm for skin fibrosis in stiff skin syndrome."

While it remains unknown what triggers similar molecular events in scleroderma, these findings do suggest a number of potential treatment strategies, says Dietz.

This study was funded by the Scleroderma Research Foundation, Howard Hughes Medical Institute, Smilow Center for Marfan Syndrome Research, National Marfan Foundation, the National Institutes of Health and Shriners Hospital for Children.

Authors on the paper are P. J. Couke and A. De Paepe of Ghent University, Belgium; D. Riegert-Johnson of Mayo Clinic, Jacksonville, Florida; S. Iqbal, P. Whiteman and P. Handford of University of Oxford; V. McConnell of Northern Ireland Regional Genetics Centre, Belfast, Ireland; C. R. Chillakuri and H. J. Mardon of John Radcliffe Hospital, Headington, UK; D. Macaya of GeneDx, Gaithersburg, Maryland; E. C. Davis of McGill University, Montreal, Canada; D. R. Keene and L. Y. Sakai of Shriners Hospital for Children, Portland, Oregon; B. L. Loeys, E. E. Gerber, D. P. Judge, F. Wigley and Dietz of Johns Hopkins.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Journal Reference:

  1. B. L. Loeys, E. E. Gerber, D. Riegert-Johnson, S. Iqbal, P. Whiteman, V. McConnell, C. R. Chillakuri, D. Macaya, P. J. Coucke, A. De Paepe, D. P. Judge, F. Wigley, E. C. Davis, H. J. Mardon, P. Handford, D. R. Keene, L. Y. Sakai, H. C. Dietz. Mutations in Fibrillin-1 Cause Congenital Scleroderma: Stiff Skin Syndrome. Science Translational Medicine, 2010; 2 (23): 23ra20 DOI: 10.1126/scitranslmed.3000488

Cite This Page:

Johns Hopkins Medical Institutions. "Causes found for stiff skin conditions." ScienceDaily. ScienceDaily, 20 March 2010. <www.sciencedaily.com/releases/2010/03/100319202530.htm>.
Johns Hopkins Medical Institutions. (2010, March 20). Causes found for stiff skin conditions. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2010/03/100319202530.htm
Johns Hopkins Medical Institutions. "Causes found for stiff skin conditions." ScienceDaily. www.sciencedaily.com/releases/2010/03/100319202530.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins