From colds to deadly lung diseases, one protein plays key role

by Dan Meyers, University of Colorado, and Tom O’Connor, UNMC public relations

sisson 

Joe Sisson, M.D. 

Joe Sisson, M.D., a UNMC clinician-scientist, was part of an international team of researchers that has zeroed in on a protein that plays a key role in many lung-related ailments, from seasonal coughing and hacking to more serious diseases such as MRSA infections and cystic fibrosis.

The finding, which was reported in the current issue of the journal Nature, advances knowledge about this range of illnesses and may point the way to eventually being able to prevent infections such as MRSA. The researchers on the study hailed from several states, as well as Mexico and England.

The key protein is called MUC5B. It’s one of two sugar-rich proteins, with similar molecular structure, that are found in the mucus that normally and helpfully coats airway surfaces in the nose and lung. The other is MUC5AC.

“We knew these two proteins are associated with diseases in which the body produces too much mucus, such as cystic fibrosis, asthma, pulmonary fibrosis and COPD,” said Chris Evans, Ph.D., an associate professor in the University of Colorado School of Medicine and the lead author on the study. “We also knew that many patients with asthma or COPD have as much as 95 percent less MUC5B in their lungs than healthy individuals, so we wanted to see if one of these is the bad player in chronic lung diseases.”

The researchers compared mice that lacked one or the other of the proteins. The animals without MUC5B got sick. Those that lacked MUC5AC were fine.

Dr. Sisson, the Larson Professor of Medicine and chief of the UNMC pulmonary, critical care, sleep and allergy section, has been involved in the study over the past two years.

A pulmonologist and NIH-funded cilia investigator, Dr. Sisson’s role was to determine the importance of ciliary motility in mice lacking MUC5B. Cilia are motorized finger-like projections of the cells that line the windpipe and bronchial tubes of the lungs. When cilia beat they create an escalator-like motion producing waves that lift mucus up and out of the lung. This function is called mucociliary clearance and is critical for normal lung health.

“We established that MUC5B is a really important component of the lung’s mucociliary clearance system,” Dr. Sisson said. “If you don’t have MUC5B, airway clearance fails even though airway cilia motility appears to be normal.”

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