Piezo2 Inhibition Shows Promise in Slowing Lung Fibrosis Progression

Philadelphia, March 25, 2025 - A study published in *The American Journal of Pathology* indicates that inhibiting Piezo2, a receptor sensing mechanical forces like stress and stiffness, may slow the progression of lung fibrosis and other fibrotic diseases. Researchers at Virginia Commonwealth University investigated Piezo2's role in pulmonary fibrosis, using tissue from IPF [Idiopathic Pulmonary Fibrosis] patients, mouse models, and cell cultures. Investigators found Piezo2 highly expressed in human lung tissue from IPF patients and in mouse models of lung fibrosis. It is also highly expressed in primary human lung fibroblasts, cells involved in fibrosis. Lung fibroblasts on stiffer substrates were reprogrammed to be more profibrotic. Inhibition of Piezo2, using RNA silencing or a peptide inhibitor, reduced profibrotic programming. Patricia J. Sime, MD, lead investigator, suggests that inhibiting Piezo2 expression or function could offer a new therapeutic approach for treating lung fibrosis and other fibrotic diseases. Margaret A.T. Freeberg, PhD, first author, notes that blocking Piezo2 signaling represents a new pathway to target in the fight against fibrosis, especially given the limitations of current treatments like nintedanib and pirfenidone.