Researchers have uncovered that extracellular vesicle communication may be the mechanism behind the propagation of lung fibrosis in patients with systemic sclerosis, according to a novel study published by Mouawad et al in Arthritis & Rheumatology. Researchers isolated extracellular vesicles from normal lungs or systemic sclerosis–derived human lungs and primary lung fibroblasts, as well as human fibrotic lungs and transforming growth factor beta–induced primary lung fibroblasts. They then assessed the extracellular vesicles’ potency by using functional assays in vitro and in vivo mouse lungs. The researchers discovered that systemic sclerosis–derived lungs and primary lung fibroblasts had a larger output of extracellular vesicles and increased fibrotic activity in these structures than normal lungs. For transforming growth factor beta–induced normal lung cores with primary lung fibroblasts, they noted increased packaging of fibrotic proteins such as fibronectin, collagen, and transforming growth factor beta into the extracellular vesicles that had been released. The researchers determined that extracellular vesicles were responsible for inducing a fibrotic phenotype in recipient primary lung fibroblasts and in vivo mouse lungs. In the mouse models, investigators were capable of reducing lung fibrosis severity by suppressing the process of extracellular vesicle release. The researchers concluded that more studies may be needed to identify viable therapeutic targets to reduce extracellular vesicle release, activity, and fibrotic cargo—and ultimately improve patient outcomes.
August 03, 2023