We reported that alveolar epithelial cells and macrophages undergo cellular senescence in the lungs of bleomycin-induced pulmonary fibrosis model mice. However, the effect of each cell senescence on fibrosis has not been clarified. In this study, we investigated changes in the expression of fibrosis-related factors using senescent cells in which p16, an important cellular senescence-inducing factor, was forcibly expressed using lentivirus vector.
　In the experiment, human alveolar epithelial cell A549 and human monocytic leukemia cell THP1 differentiated into macrophage by phorbol ester treatment were used. In A549 cells, the expression of fibrosis-promoting factors such as α-smooth muscle actin and fibronectin was increased in the cells forcibly expressing p16 as compared with the cells in which the lentiviral vector was not introduced. On the other hand, macrophage is classified into M1 type involved in inflammation and M2 type involved in repair, and it is known that an excessive increase in M2 type promotes fibrosis. In macrophages that forcibly expressed p16, decreased expression of M1 marker and increased expression M2 marker gene were observed. From the above results, it was suggested that cell senescence promotes pulmonary fibrosis by changing the expression level of fibrosis-related factors.