Sex difference in mRNA expressions of lungs post bleomycin-induced acute lung injury

The biological processes with the most divergent expression patterns included proteolysis (GO:0006508) and immune response (GO:0006955). Cellular components included both membrane and extracellular space (GO:0016020, GO:0005615), and molecular functions included protein binding (GO:0005515). KEGG pathway analysis further highlighted the contrast.

Direct comparison between females and males revealed divergent pathways, including: cytokine-cytokine receptor interaction (ko04060), complement and coagulation cascades (ko04610), and ECM-receptor interaction (ko04512). A more granular analysis of the DEGs comprising these divergent functional categories and pathways identified male lungs selectively upregulating chemokines (Cxcl10, Cxcl11, Ccl17), complement/coagulation factors, (F7, Plg, C1qa), and components of the acute-phase protease inhibitor system (Timp1, Serpina3a, Tmprss9), whereas females induced BMP signaling genes (Bmpr2, Smad9, Bmp6) and an integrin scaffolding proteins (Itga1/2/9/11, Itgb3, Flrt3) .

Notable findings from within-sex analyses showed females with enriched GO and KEGG themes related to extracellular matrix organization and cell-cycle progression, while males were more focused on immune pathways, specifically cytokine induction and viral response modules. A complete list of all DEGs across comparisons is provided in the supplementary materials.