Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A possible role for Smurf1 in pulmonary arterial hypertension

22.06.2010
Pulmonary arterial hypertension (PAH) is a progressive disease, marked by shortness of breath and fatigue which can be fatal if untreated. Increased pressure in the pulmonary artery and its branches is associated with dysfunctional growth control of endothelial and smooth muscle cells leading to excessive thickening of the blood vessel wall, obliteration of the lumen and right heart failure.

BMP (bone morphogenetic protein) receptors play an important role in preventing excess growth of vascular cells. Some individuals with PAH have mutations in BMP receptor (type II). Mutant, and to a lesser extent wild type, receptors are thought to decline in response to disease associated factors such as hypoxia and cytokines. However, the mechanisms leading to the decline in these receptors are not understood.

In the July 2010 issue of Experimental Biology and Medicine, Drs. Murakami, Mathew, Huang, Farahani, Peng, Olson and Etlinger at New York Medical College in Valhalla, NY found that a protein called Smurf1 is elevated in animal models of PAH. This protein is a ubiquitin ligase which can covalently attach ubiquitin to BMP receptors as well as regulate downstream signaling molecules. Such ubiquitin "tagging" leads to receptor endocytosis and degradation by proteasomes and/or lysosomes. Recent studies on cancer cell metastasis have linked Smurf1 with the RhoA/ROCK signaling pathway which has also been implicated in vasoconstriction and vascular remodeling in PAH. Thus, Smurf-1 may have even a broader role in PAH pathogenesis.

The researchers produced PAH in rats by treating with a chemical monocrotaline and in mice by exposure to hypoxia, two well established animal models for the disease. Increased levels of Smurf1 appeared in vascular tissue and could be visualized in endothelial and smooth muscle cells with a time course consistent with a casual role in PAH. Studies with cultured cell lines confirmed Smurf1 dependent degradation of BMP receptors. A mutated Smurf1 which lacked the ability to ligate ubiquitin was able to block BMP receptor degradation acting in a dominant negative manner. Murakami said "these results suggest that Smurf1 may be an attractive therapeutic target to block with agents like dominant negative Smurf-1 mutant or with siRNA constructs etc." Currently treatments for PAH can offer some amelioration of symptoms but no cure is available. Interfering with Smurf1 may offer promise in this regard but future research will need to confirm the role of Smurf1 in human PAH as well as explore the specificity of its actions.

Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said "Murakami et al have demonstrated an elevation of Smurf 1, a ubiquitin ligase, in rat models of pulmonary arterial hypertension (PAH). Further they have demonstrated that Smurf1 can degrade BMP receptors that have a known relationship to PAH. This suggests that elevation of Smurf1 may play a role in the molecular basis of PAH".

Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit www.sebm.org. If you are interested in publishing in the journal please visit www.ebmonline.org.

Dr. Koko Murakami | EurekAlert!
Further information:
http://www.nymc.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

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

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>