Researchers at Duke University Medical Center have found out how mouse basal cells that line airways "decide" to become one of two types of cells that assist in airway-clearing duties. The findings could help provide new therapies for either blocked or thinned airways.

鈥淥ur work has identified the Notch signaling pathway as a central regulatory 鈥榮witch鈥� that controls the differentiation of airway basal stem ,鈥� said Jason Rock, Ph.D., lead author and postdoctoral researcher in Brigid Hogan's cell biology laboratory. 鈥淪tudies like ours will enhance efforts to develop effective genetic, cellular, and molecular therapies for airway diseases - a leading cause of death worldwide.鈥�
 
The work was published in Cell Stem Cell on June 3.
 
Together with the current 铿乶dings, recent studies suggest that the Notch represents a potential therapeutic target for airway remodeling and lung disease, he said. 鈥淣otch is like an executive software package that helps to maintain the delicate balance of the epithelium, the lining of the airway,鈥� said senior author Brigid Hogan, Ph.D., chair of the Duke Department of Cell Biology. 鈥淭he plays a role in other parts of the body, including neural stem cells, and this is the first time we have seen the results of the Notch pathway in airways. We have also found that the function of Notch signaling is conserved in from human airways.鈥�
 
dictates whether the daughters of basal stem cells assume one of two different fates, Hogan said. Sustained, high levels of Notch pathway activation result in more secretory cells. These make the needed amount of mucus to move out particles that need to be cleared. Low levels of Notch signal lead to ciliated cells, which act as brushes to move the mucus along toward clearance. Notch, however, isn鈥檛 required for basal to proliferate and make additional basal cell daughters.
 
Airway disease, including chronic obstructive pulmonary disease, cystic fibrosis, asthma, acute allergies, and transplant complications, can range from fatal to debilitating, so understanding the secrets of how healthy cells can grow, and in the proper amounts, after injury is important. Fifty-five percent of deaths from lung disease result from changes in the small airways, Hogan said.
 
The researchers also demonstrated in this work that the smallest airway branches in humans are the same size and are organized like the largest (tracheal) tubes in mice. The next step for the team is to investigate the behavior of the daughters of basal cells to learn what machinery is involved in making them commit to various lineages, and how this system is coordinated to help restore lung function, Hogan said.

Provided by Duke University