Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Causes Found for Stiff Skin Conditions

24.03.2010
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 this week 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.

On the Web:
Harry C. Dietz
http://www.hopkinsmedicine.org/geneticmedicine/people/faculty/dietz.html
William S. Smilow Center for Marfan Syndrome Research http://www.hopkinsmedicine.org/geneticmedicine/Clinical_Resources/Smilow_Marfan/smilow.html
Johns Hopkins Scleroderma Center
http://scleroderma.jhmi.edu/
Hopkins Medicine Today http://www.hopkinsmedicine.org/mediaII/index.html is the online news site that links you to the latest news, features, videos and podcasts from around Johns Hopkins Medicine

Audrey Huang | idw
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>