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 Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel

nachricht Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>