Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular trigger for Cerebral Cavernous Malformation identified

26.11.2015

Researchers in Italy, Germany and the United States have identified a regulatory protein crucial for the development of Cerebral Cavernous Malformation – a severe and incurable disease mainly affecting the brain microvasculature. The results, which are published in EMBO Molecular Medicine, show that the KLF4 protein plays a central role in the development of CCM lesions.

Cerebral Cavernous Malformation (CCM) is caused by mutations in the CCM1, CCM2 or CCM3 genes, and is characterized by vascular lesions that can lead to cerebral haemorrhage. Previous research has shown that ablation of CCM1 in mice leads to CCM pathology via a mechanism called Endothelial-to-mesenchymal transition (EndMT). While considerable effort has gone into establishing that EndMT occurs and plays a role in a variety of pathologic conditions, its molecular triggers have not been well defined.

The scientists found that KLF4 – a zinc-finger transcription factor of the Kruppel-Like Factor family – is strongly upregulated in the lesions of CCM1 knockout mice.

“Our study demonstrates that the genetic inactivation of KLF4 blocks the development and progression of CCM lesions and prevents mouse mortality due to brain haemorrhage,” says EMBO Member Elisabetta Dejana of the Italian FIRC Institute of Molecular Oncology and the University of Milan, the corresponding author of the study. KLF4 functions as one of the reprogramming “Yamanaka factors” in pluripotent stem cell induction cocktails.

The CCM pathway is required in endothelial cells for normal cardiovascular development and to prevent postnatal vascular malformations. The malformations are usually located in the white matter (cortex) of the brain. CCM are present in up to 0.5% of the general population, and they account for a large proportion (8-15%) of all brain and spinal vascular malformations.

Presently, there are no pharmacological treatments to prevent development or reduce the size of existing CCMs. The study identifies novel potential pharmacological targets to prevent the progression of this disease.

The study was conducted by researchers of the Italian FIRC Institute of Molecular Oncology and the University of Milan, in collaboration with the Max Planck Institute for Molecular Medicine in Munster, Germany, University Hospitals Case Medical Center in Cleveland and University of Virginia, United States, and with the support of Telethon and the Italian Association for Cancer Research (AIRC).

KLF4 is a key determinant in the development and progression of Cerebral Cavernous Malformations

Roberto Cuttano, Noemi Rudini, Luca Bravi, Monica Corada, Costanza Giampietro, Eleanna Papa, Marco Francesco Morini, Luigi Maddaluno, Nicolas Baeyens, Ralf H.
Adams, Mukesh K. Jain, Gary K. Owens, Martin Schwartz, Maria Grazia Lampugnani and Elisabetta Dejana

Read the paper: http://embomolmed.embopress.org/cgi/doi/10.15252/emmm.201505433

doi: 10.15252/emmm.201505433

Further information on EMBO Molecular Medicine is available at www.embomolmed.embopress.org

Media Contacts
Yvonne Kaul
Communications Officer
yvonne.kaul@embo.org

Roberto Buccione
Editor, EMBO Molecular Medicine
Tel: +49 6221 8891 412
roberto.buccione@embo.org

About EMBO
EMBO is an organization of more than 1700 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work.

EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and scientific journals disseminate the latest research and offer training in techniques to maintain high standards of excellence in research practice. EMBO helps to shape science and research policy by seeking input and feedback from our community and by following closely the trends in science in Europe. 
For more information: www.embo.org

Weitere Informationen:

http://www.embo.org/news/research-news/research-news-2015/molecular-trigger-for-...

Yvonne Kaul | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Antimicrobial substances identified in Komodo dragon blood
23.02.2017 | American Chemical Society

nachricht New Mechanisms of Gene Inactivation may prevent Aging and Cancer
23.02.2017 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

From rocks in Colorado, evidence of a 'chaotic solar system'

23.02.2017 | Physics and Astronomy

'Quartz' crystals at the Earth's core power its magnetic field

23.02.2017 | Earth Sciences

Antimicrobial substances identified in Komodo dragon blood

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>