Study Points to ABCC1 as Potential Therapy Target in COPD, Asthma
A protein called ABCC1 lets a specific signaling molecule leak out of muscle cells in the airways, which may contribute to the airway constriction that makes it harder for people with asthma or chronic obstructive pulmonary disease (COPD) to breathe, a recent study reported.
“This protein has been recognized as important in some diseases, but it has never been defined before in airway diseases, such as asthma and COPD, until now,” Reynold Panettieri, MD, vice chancellor of translational medicine at Rutgers University and a co-author of the study, said in a press release.
These findings, Panettieri said, “could be potentially very important in improving asthma and COPD management.”
The study, “Inhibition of ABCC1 Decreases cAMP Egress and Promotes Human Airway Smooth Muscle Cell Relaxation,” was published in the American Journal of Respiratory Cell and Molecular Biology.
Cyclic adenosine monophosphate, or cAMP for short, is a signaling molecule that normally acts inside of muscle cells to promote relaxation.
Now, a team led by scientists at Rutgers, in New Jersey, found that cAMP can “leak” out of airway muscle cells, particularly in the context of disease, making them prone to constrict.
The team found abnormally high cAMP levels in the blood of a small group of people with asthma. This finding suggests that measuring the levels of this signaling molecule may be useful in helping to diagnose respiratory diseases, the researchers said.
“The presence of too much cAMP in a patient’s blood is a new biomarker that can help characterize specific types of asthma and COPD,” Panettieri said.
Further experiments using cell models revealed that the protein ABCC1 was involved in the leakage of cAMP. Blocking this protein — either pharmacologically or by genetic manipulation — prevented cAMP from leaking, the scientists found. Notably, blocking ABCC1 also reduced the tone of muscle cells, and made them more prone to relax.
“We demonstrated that if you decrease the leakage [of cAMP], the smooth muscles in the airways relax,” Panettieri said.
In COPD and asthma, airway muscles tend to constrict too much, causing the airways to become unusually narrow and making breathing difficult. As such, relaxing airway muscles by blocking ABCC1 could help to ease breathing and make bronchodilators more effective, according to Panettieri.
“These findings identify a previously unrecognized role for ABCC1 in the … regulation of [cAMP] in [human airway smooth muscle cells],” the researchers wrote.
Panettieri said the findings will help clinicians better identify and determine the severity of chronic lung diseases such as COPD.
“This knowledge allows for better diagnostics of the illness and forms the basis for new therapeutics that will plug the leak of cAMP in the protein,” Panettieri said.
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