Dual roles of fibroblast-epithelial crosstalk in acute and chronic lung injury

Dysfunctional interactions between fibroblasts and epithelial cells contribute to the progression of chronic lung diseases, including idiopathic pulmonary fibrosis. Our findings showed that chronic epithelial damage initiates a bidirectional fibrotic cascade between the epithelium and lung fibroblasts, leading to further epithelial damage and the release of pro-fibrotic mediators. Conversely, our transcriptomic and proteomic analyses highlighted that, in the context of acute epithelial injury, a protective signaling environment merges that mitigates further damage. We observed that epithelial cells shift their metabolism towards increased aerobic fatty acid metabolism, promoting healing and repair. By delineating secreted regulators responsible for inducing these positive responses, we identified pentraxin 3 (PTX3) as a top hit harboring antifibrotic characteristics.