Specialized blood vessel cells found to actively drive lung fibrosis

Millions of people worldwide are affected by diseases that cause scarring of the lungs, often leading to breathing difficulties and reduced quality of life. Progressive scarring of the lungs can severely impair breathing and is a hallmark of many chronic lung diseases, most notably pulmonary fibrosis, for which treatment options remain very limited and ineffective.

A new collaborative study from the laboratories of Drs. Xaralabos Varelas and Giovanni Ligresti from Boston University Chobanian & Avedisian School of Medicine have identified a distinct population of cells located in lung veins that becomes active after injury and helps create an environment that promotes scar tissue formation, a process known as fibrosis. Identifying a previously unrecognized driver of lung fibrosis and a signaling pathway that can be targeted, offers new opportunities for developing therapies to prevent, or slow disease progression in pulmonary fibrosis and other fibrotic lung diseases.

Our findings suggest that the lung's blood vessels are not simply bystanders in fibrosis but may actively drive disease through changes in the specialized cells that line the lung vasculature."

Kostas Kontodimas, first author, graduate student, department of biochemistry and cell biology, Boston University Chobanian & Avedisian School of Medicine

The researchers investigated how lung scarring begins and whether the cells that line blood vessels contribute to abnormal scar formation. They used genetically engineered experimental models and advanced laboratory techniques to selectively inactivate genes that preserve normal vascular cell function. They then tracked how the lungs changed over time. They also analyzed thousands of individual lung cells to identify which cell types were affected and how they communicated with one another during scar formation and progression. Finally, the team tested a drug that blocks the overactive signaling pathway and found that this approach could prevent lung scarring while reducing inflammation and blood vessel damage in preclinical models.

Beyond its implications for lung scarring, the scientists believe this study challenges the traditional view that the cells lining blood vessels primarily serve as passive conduits for delivering oxygen and nutrients. "Our findings suggest that specialized blood vessel cells actively communicate with surrounding tissues and can influence how diseases begin and progress. This raises the possibility that similar populations of blood vessel cells may play important roles in other diseases involving chronic inflammation or tissue scarring, opening new avenues for research across a wide range of conditions," adds corresponding author Varelas, a professor of biochemistry and cell biology.

Although additional studies are needed to determine whether these findings translate to people, the work provides important insight into how pulmonary fibrosis develops, and could ultimately lead to more effective treatments for this devastating disease.

These findings appear online in the journal Science Advances.