Novel molecular target to prevent scarring of the lung blood vessels identified

June 13, 2018, Brigham and Women's Hospital
Nucleus of human pulmonary artery endothelial cell treated with aldostrerone (10?7 M) for 24 hours shows co-localization of NEDD9 (red) and NKX2-5 (green), DAPI (blue), 63x. Credit: Bradley Maron, Brigham and Women's Hospital

Pulmonary arterial hypertension, a severe form of cardiopulmonary disease in which the arteries that transport blood from the heart to the lungs become thickened, constricted, and scarred, is a disease for which there is no cure. Investigators from Brigham and Women's Hospital are unraveling the molecular mechanisms that may control PAH's development and progression in an effort toward finding treatments that can halt the disease's advancement.

In a paper published this week in Science Translational Medicine, researchers share results from a study that identifies the cancer NEDD9 as a critical player in disease development, with potential therapeutic implications for patients with PAH.

"Our work identifies as a novel molecular target to prevent in lung arteries, which can lead to early right-sided heart failure and death," said corresponding author Bradley Maron, MD, a cardiologist and vascular biologist at BWH. "Our data provide an alternative mechanism that may account for the variability in fibrosis observed across subgroups of patients with PAH."

In PAH, fibrosis (scarring) is an important cause of damage to pulmonary arteries, which increases strain on the heart and leads to perpetual shortness of breath. In the past, researchers had theorized that one pathway acted as a "master switch" to globally control fibrosis but new evidence suggests that the development of fibrosis may be more complicated and more specific to different kinds of tissue. To better understand which genes and proteins may influence scarring specifically in the lung , the Brigham research team used network medicine—a method of mapping relationships between proteins, pathways and more. Through this approach, the researchers discovered that the cancer protein NEDD9 is a critical mediator of vascular fibrosis in lung blood vessels.

They went on to identify a specific amino acid residue in NEDD9 that controls lung artery fibrosis. In patients with PAH, increased oxidant stress modifies this NEDD9 amino acid to cause lung artery fibrosis. The team also showed that the artery endothelium, previously regarded largely as a bystander in vascular fibrosis, contributes to this problem.

At the heart of the research team's findings is NEDD9, which their data suggest mediates fibrotic vascular remodeling. The authors note that this has potential therapeutic relevance for PAH patients. While a therapy that targets this protein has not yet been developed, because of its role in cancer, several studies have put NEDD9 forward as an important therapeutic target for future drug discovery efforts.

Explore further: Blocking the molecular source of idiopathic pulmonary fibrosis

More information: A.O. Samokhin el al., "NEDD9 targets COL3A1 to promote endothelial fibrosis and pulmonary arterial hypertension," Science Translational Medicine (2018). stm.sciencemag.org/lookup/doi/ … scitranslmed.aap7294

Related Stories

Blocking the molecular source of idiopathic pulmonary fibrosis

May 8, 2018
Idiopathic pulmonary fibrosis (IPF) is one of the most challenging and frustrating diseases that pulmonologists face.

Lung-on-a-chip simulates pulmonary fibrosis

May 25, 2018
Developing new medicines to treat pulmonary fibrosis, one of the most common and serious forms of lung disease, is not easy.

Restoring lipid synthesis could reduce lung fibrosis

March 6, 2018
Pulmonary fibrosis, an ongoing process of scarring that leaves patients chronically short of breath, can progress in severity until the only course of treatment is lung transplant. A new study shows that restoring the lipids ...

Study identifies new target for treatment of pulmonary hypertension

April 30, 2018
Scientists at Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago have identified a gene called FoxM1 as a promising target for treatment of pulmonary hypertension, or high ...

Protein molecule may improve survival in deadly lung disease

May 6, 2014
Researchers at the University of Illinois at Chicago College of Medicine have discovered a protein molecule that seems to slow the progression of pulmonary fibrosis, a progressive lung disease that is often fatal three to ...

Thyroid hormone therapy heals lung fibrosis in animal study

December 4, 2017
Thyroid hormone therapy significantly resolves fibrosis, or scarring, in the lungs of mice, increasing their survival from disease, a Yale-led study shows. These provide a novel insight into the development of pulmonary fibrosis ...

Recommended for you

A versatile vaccine that can protect mice from emerging tick-borne viruses

December 18, 2018
A group of researchers led by Michael Diamond of Washington University School of Medicine in St. Louis have developed a vaccine that is effective in mice against Powassan virus, an emerging tick-borne virus that can cause ...

How cholera bacteria make people so sick

December 18, 2018
The enormous adaptability of the cholera bacterium explains why it is able to claim so many victims. Professor Ariane Briegel from the Leiden Institute of Biology has now discovered that this adaptability is due to rapid ...

Green leafy vegetables may prevent liver steatosis

December 17, 2018
A larger portion of green leafy vegetables in the diet may reduce the risk of developing liver steatosis, or fatty liver. In a study published in PNAS researchers from Karolinska Institutet in Sweden show how a larger intake ...

Discovery of novel mechanisms that cause migraines

December 17, 2018
Researchers at CNRS, Université Côte d'Azur and Inserm have demonstrated a new mechanism related to the onset of migraine. They found how a mutation that causes dysfunction in a protein which inhibits neuronal electrical ...

RNA processing and antiviral immunity

December 14, 2018
The RIG-I like receptors (RLRs) are intracellular enzyme sentries that detect viral infection and initiate a first line of antiviral defense. The cellular molecules that activate RLRs in vivo are not clear.

Faster test for Ebola shows promising results in field trials

December 13, 2018
A team of researchers with members from the U.S., Senegal and Guinea, in cooperation with Becton, Dickinson and Company (BD), has developed a faster test for the Ebola virus than those currently in use. In their paper published ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.