miR-205-5p drives endothelial dysfunction and senescence in pulmonary fibrosis

We have previously demonstrated that aging-associated vascular dysfunction drives maladaptive endothelial responses to injury and exacerbates lung fibrosis via secretion of pro-fibrotic endothelial-derived factors. However, regulatory mechanisms governing endothelial dysfunction during progressive lung fibrosis remain poorly understood.

Here, using preclinical mouse models of progressive lung fibrosis as well as human IPF lungs, we demonstrate that miR-205-5p is overexpressed in lung ECs from fibrotic lungs, and coordinates gene expression programs implicated in endothelial dysfunction and progressive fibrosis. Transcriptomic profiling revealed that miR-205-5p downregulates genes involved in cell cycle progression while upregulating multiple genes encoding secreted mediators of fibrosis and components of the senescence-associated secretory phenotype, that recapitulating the aberrations observed in lung ECs isolated from human IPF lungs.