Lumikine Attenuates Ventilation-Induced Lung Injury in Mice with Lipopolysaccharide-Induced Lung Fibrosis

Lipopolysaccharide (LPS) induces pulmonary fibrosis by increasing microvascular permeability and inducing severe inflammation and extracellular matrix accumulation. Mechanical ventilation (MV), although life-sustaining, can increase inflammatory cytokine production, oxidative stress, and alveolar–capillary membrane permeability, leading to ventilator-induced lung injury and pulmonary fibrosis. Lumican is essential for extracellular matrix signaling and wound fibrogenesis in the lungs, cornea, and heart. Lumikine, a peptide corresponding to the 13 C-terminal amino acids of lumican, binds to transforming growth factor-β receptor I/activin receptor-like kinase 5 and promotes wound healing. How the lumican pathway contributes to MV-induced lung inflammation and fibrosis remains unclear. We hypothesized that MV with or without LPS pretreatment would exacerbate lung injury, oxidative stress, and lung fibrosis through the lumican pathway. C57BL/6 mice (wild-type and lumican-deficient) were injected with LPS (intratracheal; 7 days) to induce lung fibrosis and then subjected to MV (10 mL/kg; room air; 8 h). Nonventilated mice served as controls. MV with LPS pretreatment reduced lumican expression and increased microvascular permeability, matrix metalloproteinase-9 level, transforming growth factor-β1 level, α-smooth muscle actin staining intensity, and Masson’s trichrome staining intensity. Lumikine substantially mitigated these fibrotic changes. In conclusion, lumikine attenuates MV-induced exacerbation of pulmonary fibrosis after LPS-induced acute lung injury, partially by modulating the lumican pathway.