Analysis of the role of macrophage senescence in lung fibrosis using macrophage-specific p16 knockout mice

Abstract

The involvement of senescent cells in the lungs of idiopathic pulmonary fibrosis has been strongly suggested. In our previous study, we confirmed cellular senescence of macrophages and expression of p16^INK4a, a key marker of cellular senescence, in the lungs from bleomycin-induced pulmonary fibrosis model mice. However, the role of macrophage senescence in fibrosis has not been clarified. In the present study, we investigated the role of macrophage senescence in lung fibrosis using macrophage-specific p16 knockout (p16 cKO) mice. While bleomycin treatment increased p16 mRNA expression in whole lung tissue from the control mice, such an effect was not observed in the p16 cKO mice. We also examined expression of p16 mRNA in macrophages isolated from the lung and confirmed that the levels were below the detection limit in p16 cKO mice. However, Sirius Red staining revealed no difference in collagen accumulation by bleomycin treatment between lungs from control and p16 cKO mice. In addition, there was no difference in the soluble collagen concentrations, cell numbers or protein concentrations in bronchoalveolar lavage fluid, which are indicators of pulmonary fibrosis. These results suggest that macrophage senescence may have little effect on lung fibrosis.