Figure 1. Impaired lung fibrosis resolution in aged mice is associated with increased inflammatory, ECM remodeling, and survival gene signatures in lung fibroblasts.

(A) Young and aged Col1a1-GFP mice were exposed to saline or bleomycin and sacrificed after 30 days during early fibrosis resolution. Lungs were harvested, digested, and sorted by FACS for CD31^–CD45^–EpCAM^–GFP⁺ lung fibroblasts and used for RNA-Seq analysis (young sham, n = 2; young bleo 30 days, n = 5; aged sham, n = 4; aged bleo 30 days, n = 5). (B) Principal components analysis (PCA) displaying clusters of samples from experimental groups and the similarity of their transcriptomes. (C–E) (Left) Plots of log₁₀ (avg.RPKM) versus log₂ fold change of significantly upregulated or downregulated genes relative to young sham; fold-change ≥ 1.5, FDR ≤ 0.1. (Right) Percentage and total numbers of genes significantly upregulated (yellow) or downregulated (blue) relative to young sham. (F–H) Heatmaps of differentially regulated gene signatures showing extracellular matrix (ECM) genes (F), extracellular matrix remodeling genes (G), and prosurvival/proliferation genes (H), displayed as Z scores of RPKM.