Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


A possible role for Smurf1 in pulmonary arterial hypertension

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 If you are interested in publishing in the journal please visit

Dr. Koko Murakami | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht ‘Farming’ bacteria to boost growth in the oceans
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie

nachricht Calcium Induces Chronic Lung Infections
24.10.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Oasis of life in the ice-covered central Arctic

24.10.2016 | Earth Sciences

‘Farming’ bacteria to boost growth in the oceans

24.10.2016 | Life Sciences

Light-driven atomic rotations excite magnetic waves

24.10.2016 | Physics and Astronomy

More VideoLinks >>>