Investigating the role of aging and lung fibrosis in Endothelial Cells with RNA sequencing

In order to elucidate the contribute of the pulmonary vasculature to lung fibrosis, we injured young and aged mice with bleomycine, to create a model of resolving versus persistent lung fibrosis. The animals were sacrificed 30 days after the injury (time point in which we observed a divergent resolving vs persistent lung fibrosis in young vs aged mice). We found that lung fibrosis resolution in young mice was accompained by the activation of transcriptional programs promoting vascular repair and lung fibrosis resolution. Lung endothelial cells from aged mice after injury failed to activate these programs, leading to dysrepair and progressive fibrosis. Freshly isolated lung endothelial cells from young and aged mice either sham or after bleomycin were subjected to ATACseq analysis. A widespresd reduction in chromatin accessibility was found in aged lung endothelial cells, either sham or after bleomycin administration, compared to young endothelial cells.