@article {Kurita3243, author = {Yusuke Kurita and Jun Araya and Hiromiti Hara and Kenji Kobayashi and Saburo Ito and Naoki Takasaka and Hiroshi Wakui and Yutaka Yoshii and Shunsuke Minagawa and Jun Kojima and Takanori Numata and Kenichiro Shimizu and Makoto Kawaishi and Yumi Kaneko and Katsutoshi Nakayama and Kazuyoshi Kuwano}, title = {Transcription factor EB (TFEB) regulates cigarette smoke extract (CSE)-induced cellular senescence}, volume = {44}, number = {Suppl 58}, elocation-id = {3243}, year = {2014}, publisher = {European Respiratory Society}, abstract = {Introduction: Senescence has been implicated in the pathogenesis of COPD, and cigarette smoke is known to induce cellular senescence. One of the typical manifestations of cellular senescence is accumulation of damaged proteins and organelles, which is mainly regulated through lysosomal degradation. Recent advances demonstrate that TFEB is a central regulator of lysosomal biogenesis and cellular degradative pathways in association with autophagy machinery. Methods: Using human bronchial epithelial cells (HBEC), senescence associated beta-galactosidase staining and western blotting of p21 were performed to evaluate senescence. Fluorescence microscopic detection of mature lysosome was performed by LysoTracker staining. To characterize the autophagy-lysosomal degradation pathway, western blotting of p62, ubiquitin, and LC3 were performed. TFEB expression levels were modulated by cDNA and siRNA transfection. Results: We demonstrated that TFEB expression levels were decreased in lung homogenates from COPD patients. CSE induced HBEC senescence with concomitant decrease in TFEB. CSE-induced HBEC senescence was inhibited by TFEB overexpression, while TFEB knock down further enhanced HBEC senescence. TFEB overexpression induced activation of the autophagy-lysosomal pathway, as demonstrated by increased LC3-II conversion in western blotting and enhanced dot formation in LysoTracker staining. Conclusion: These findings suggest that TFEB-mediated activation of the autophagy-lysosomal pathway plays a key regulatory role in CSE-induced cellular senescence. Thus, sufficient levels of TFEB induction may be a novel medical intervention to prevent cellular senescence in COPD pathogenesis.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/44/Suppl_58/3243}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }