Investigating the role of aging and lung fibrosis in Endothelial Cells with RNA sequencing. 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. Overall design: 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.

为阐明肺血管系统在肺纤维化进程中的作用，我们通过博莱霉素对年轻与老年小鼠造模，构建了可消退型与持续性肺纤维化模型。于造模后30天处死实验动物——该时间点下，我们观察到年轻小鼠与老年小鼠分别呈现出可消退与持续性肺纤维化的表型差异。我们发现，年轻小鼠的肺纤维化消退过程伴随有促进血管修复与肺纤维化消退的转录程序激活。而损伤后的老年小鼠肺内皮细胞无法激活此类转录程序，最终导致血管修复异常与进行性肺纤维化。实验整体设计：从假手术处理及博莱霉素造模的年轻、老年小鼠体内新鲜分离肺内皮细胞，对其开展转座酶可及性测序（ATACseq）分析。与年轻小鼠肺内皮细胞相比，假处理组与博莱霉素给药后的老年小鼠肺内皮细胞均出现了染色质可及性的广泛降低。