Specialized Lung Vein Cells Actively Drive Pulmonary Fibrosis, Revealing a New Therapeutic Target
核心洞察
Researchers at Boston University identified a distinct population of lung vein cells that becomes active after injury and promotes scar tissue formation in pulmonary fibrosis (搜索).
The study reveals a previously unrecognized driver of lung fibrosis (搜索) and a targetable signaling pathway, offering new opportunities to prevent or slow disease progression.
Blocking the overactive signaling pathway with a drug prevented lung scarring while reducing inflammation and blood vessel damage in preclinical models.
A collaborative study from the laboratories of Drs. Xaralabos Varelas and Giovanni Ligresti at Boston University Chobanian & Avedisian School of Medicine has 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. The findings, published online in the journal Science Advances, identify a previously unrecognized driver of lung fibrosis (搜索) and a signaling pathway that can be targeted, offering new opportunities for developing therapies to prevent or slow disease progression in pulmonary fibrosis (搜索) and other fibrotic lung diseases.
Progressive scarring of the lungs can severely impair breathing and is a hallmark of many chronic lung diseases, most notably pulmonary fibrosis (搜索), for which treatment options remain very limited and ineffective. Millions of people worldwide are affected by diseases that cause scarring of the lungs, often leading to breathing difficulties and reduced quality of life.
"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," explained first author Kostas Kontodimas, a graduate student in the department of biochemistry and cell biology.
Investigating the Origins of Lung Scarring
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, then tracked how the lungs changed over time. The team 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 researchers 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.
Challenging a Long-Held View of Blood Vessel Cells
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," added 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 (搜索) develops, and could ultimately lead to more effective treatments for this devastating disease.