Ivacaftor, a drug used to treat cystic fibrosis, reduced collagen buildup in the lungs of mice injured with a chemical called bleomycin. The researchers also found lower levels of markers linked to cellular senescence in mouse lungs and in lab-grown cultures of mouse lung cells.
The findings come from a study published October 31 in Cell Death Discovery. The journal released the peer-reviewed accepted manuscript ahead of the final version.
Evidence level Early Research. The drug experiments used mice and lab-grown cells. Whether ivacaftor can treat pulmonary fibrosis in people remains open.
How much scarring did the mice develop?
Pulmonary fibrosis occurs when excess collagen and other material build up in the lungs, stiffening tissue around the tiny air sacs where oxygen enters the blood. To model that process, researchers gave male mice bleomycin on days 0, 3 and 7. Daily oral ivacaftor or its oil vehicle began on day 14, one week after the last bleomycin dose. The main tissue measurements were made on day 28.
Lung sections from treated mice showed less collagen staining. In a separate analysis of those sections, about 19% of cells stained positive for type I collagen in the ivacaftor group, compared with about 41% in the vehicle group. Figure 3D shows four mice per injured group. These percentages are estimates from the plotted means and describe the staining readout.
On the 0-to-8 Ashcroft scale, where higher scores indicate more severe scarring, the mean score was about 3.5 with ivacaftor and 5.5 with vehicle. Figure 1E plots 14 treated and 20 vehicle-treated mice in that comparison. The researchers also measured lower hydroxyproline, a collagen-related amino acid, in blood plasma. A separate experiment that continued treatment through day 42 also found lower scarring scores.
Why the lung’s repair cells matter
Alveolar type 2 cells make surfactant, which reduces surface tension and helps keep the air sacs open. After injury, these cells can multiply and give rise to the thin type 1 cells that form most of the surface used for gas exchange.
The researchers focused on CFTR, a channel that moves chloride and bicarbonate ions across cell membranes and helps regulate fluid at epithelial surfaces. Ivacaftor increases the chance that the channel stays open. When the team deleted the Cftr gene specifically in type 2 cells, the drug no longer produced a clear reduction in scarring scores. The scores fell in littermates with intact CFTR. That separate experiment used two bleomycin doses and four mice per group for the scarring analysis, supporting a role for CFTR in those repair cells.
What the cells and human tissue showed
Senescent cells stop dividing and can release signals that promote inflammation and scarring. Ivacaftor lowered several markers linked to this state in injured mouse lungs, including p21 protein. In three-dimensional cultures grown from mouse type 2 cells, ivacaftor also reduced the number of cells positive for markers such as p16. The cultures received the drug alongside bleomycin. Our earlier coverage of an experimental vaccine targeting senescent cells describes a different approach to studying these cells in mice.
Separately, the team examined lung tissue from people with idiopathic pulmonary fibrosis and from donors without lung disease. Type 2 cells with senescence markers appeared more often in the fibrotic tissue. The donor comparison was observational. In mice, scarring after bleomycin can resolve on its own, and this study used only males. The human tissue findings leave open whether the drug can help people with pulmonary fibrosis.
Primary source and reporting notes
Wu S, Yang L, Ma Y and colleagues. Pharmacologic CFTR potentiation attenuates alveolar epithelial senescence and experimental pulmonary fibrosis. Cell Death Discovery, October 31, 2026. The reporting draws on the accepted manuscript and supplementary methods. The manuscript gives conflicting accounts of whether mice were randomized, although it specifies that researchers scoring lung scarring were blinded to the treatment groups.
Illustration of lung air sacs and surrounding collagen fibers. Researchers tested ivacaftor in mice with chemically induced lung fibrosis.