discoveries magazine

Breathing Room

Cedars-Sinai investigators have identified a major cause of pulmonary fibrosis, a mysterious and deadly disease that scars the lungs and obstructs breathing. The disease, which has no known cure, appears to result from the failure of lung stem cells that help airways recover from injury.

Led by Paul W. Noble, MD — chair of the Department of Medicine, director of the Women’s Guild Lung Institute, and the Vera and Paul Guerin Family Distinguished Chair in Pulmonary Medicine — with research scientist Carol Liang, MD, the study focused on alveoli, tiny air sacs in the lung that are vital to breathing. Alveoli are lined with cells that normally produce a substance to keep the air spaces open. In pulmonary fibrosis, they become abnormal, building up fibrous tissue in the lungs.

While previous research has been unable to explain why this happens, the Cedars-Sinai team found an answer in stem cells known as AEC2s. These cells are critical to repairing and regenerating epithelial cells in adult lungs.

In people with pulmonary fibrosis, something goes wrong with AEC2 cells. The study revealed that lung tissue from patients with the disease had far fewer of these cells than normal, and the AEC2 cells that were there were less able to regenerate. The investigators determined that this is likely due to lower concentrations of hyaluronan, a chemical substance that sits on the cell surface and promotes tissue repair and renewal. Further, in laboratory mice, the team discovered that deleting this substance produced the type of scarring found in pulmonary fibrosis after lung injury.

Additional studies will explore how hyaluronan affects fibrosis — and how it might be restored in patients who need it.