SERPIN B3/B4, members of the
serpin superfamily, are fundamental for the control of proteolysis through a known inhibitory function of different
proteases. Several studies have documented an important role of
SERPIN B3 in the modulation of
inflammation, programmed cell death and
fibrosis. To confirm the role of
SERPIN B3 in lung
fibrosis and overall investigate its influence on epithelial dysfunction, a stratified controlled trial randomly assigning
bleomycin (BLM) treatment was performed on both
SERPIN B3 transgenic (TG) and wild-type (WT) mice. TG and WT animals were killed 48 h (group T48 h) and 20 days (group T20d) after BLM treatment. Lung
fibrosis was assessed by histology and
hydroxyproline measurement. Architectural remodeling,
inflammation, epithelial apoptosis and proliferation were quantified. Moreover, the profibrogenetic
cytokine transforming growth factor (TGF)-β,
cathepsin K, L and S were also investigated. No significant differences were observed between TG and WT mice of group T48 h in any parameters. In group T20d, less
inflammation and a significant increase in epithelial proliferation were detected in treated TG than WT mice despite a similar apoptotic index, thus resulting in a different apoptosis/proliferation imbalance with a significant gain of epithelial proliferation. Moreover, TG mice showed higher TGF-β expression and more extended
fibrosis. General linear model analysis, applied on morphological data, showed that interaction between
SERPIN B3 expression and treatment was mainly significant for
fibrosis. This study provides in vivo evidence for a role of
SERPIN B3 in inhibiting
inflammation and favoring epithelial proliferation with increased TGF-β secretion and thus the likelihood of consequent fibrogenesis.