Pseudomonas (P.) aeruginosa is an opportunistic pathogen that causes serious infections and hospital-acquired pneumonia in immunocompromised patients. P. aeruginosa accounts for up to 20% of all cases of hospital-acquired pneumonia, with an attributable mortality rate of ~30–40%. The poor clinical outcome of P. aeruginosa-induced pneumonia is ascribed to its ability to disrupt lung barrier integrity, leading to the development of lung edema and bacteremia. Airway epithelial and endothelial cells are important architecture blocks that protect the lung from invading pathogens. P. aeruginosa produces a number of virulence factors that can modulate barrier function, directly or indirectly, through exploiting cytoskeleton networks and intercellular junctional complexes in eukaryotic cells. This review summarizes the current knowledge on P. aeruginosa virulence factors, their effects on the regulation of the cytoskeletal network and associated components, and molecular mechanisms regulating barrier function in airway epithelial and endothelial cells. A better understanding of these processes will help to lay the foundation for new therapeutic approaches against P. aeruginosa-induced pneumonia.

Idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), and systemic sclerosis-associated interstitial lung disease (SSc-ILD) share the same structural outcome: extracellular matrix (ECM) deposition. Whether this shared endpoint reflects shared or distinct molecular programs remains unresolved. Differential expression results from four GEO datasets representing IPF, HP, non-IPF ILD, and SSc-ILD were intersected with the 1027-gene human matrisome masterlist and classified by threshold-defined disease preference. All four diseases shared a 21-gene upregulated matrisome core, and the matrisome fraction rose with cross-disease sharing, from 4.3% of single-disease upregulated genes to 45.7% of genes upregulated in all four (significant Cochran–Armitage trend), and the enrichment persisted when any single cohort was removed. Apparent disease preference was largely attributable to unequal statistical power: of 29 genes measurable in all four datasets, 24 showed a concordant sub-threshold effect in at least one comparator disease. Category composition of the threshold-defined signatures did not differ significantly between diseases, and the exploratory pathway panel is reported within diseases only, because significance scales with cohort size. In a within-cohort comparison of IPF with chronic HP in GSE150910, with platform, cohort, and control population held constant, matrisome genes were over-represented among the 2732 genes separating the two diseases, and 205 matrisome genes distinguished them. Fibrosing ILDs share a cross-cohort ECM core, and the apparent disease preference of the remaining signatures largely reflects differences in statistical power between cohorts. Disease-preferential matrisome expression is nonetheless detectable when disease and study are not confounded, so the limitation lies in threshold-based cross-study intersection rather than in the matrisome compartment itself.