Abstract
Because cigarette smoke can induce COPD/emphysema through accelerating senescence with or without an incomplete repair system. However, the pathogenesis of COPD following lung senescence induced by CS is not fully understood. Airspace enlargement and airway epithelial cell senescence are common finding during the COPD development. We investigated the lung tress response to CS and demonstrated that a stress-responsive transcription factor, FOXO3, was regulated by deacetylase. SIRT1 inhibited FOXO3 acetylation and FOXO3 degradation, leading to FOXO3 accumulation and activation in airway epithelial cells. CS exposure activated SIRT1 contributed to FOXO3 activation and functioned to protect lungs, as deletion of SIRT1 decreased CS-induced FOXO3 activation and resulted in more severe airway epithelial cells senescence airspace enlargement. Strikingly, deletion of FOXO3 during the development of COPD aggravated lung structural and functional damage, leading to a much more profound COPD phenotype. We show that deletion of FOXO3 resulted in decreased autophagic response and increased senescence, which may explain lung protection by FOXO3. Our study indicates that in the COPD, stress-responsive transcription factors can be activated for adaptions to counteract senescence insults, thus attenuating COPD development.
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Acknowledgments
We express our gratitude to our colleagues who work in our laboratory for their cursory review of the paper as well as their insightful conversations, support and courteous assistance.
Declaration of interest
The authors declare no competing interests.
Ethics approval and informed consent
The Experimental Animal Ethics Committee of Hangzhou Medical College granted its approval to all animal experiments, which were performed in compliance with the guidelines for the Care and Use of Laboratory Animals established by Zhejiang Industry University (Hangzhou, China).
Author contributions
All authors made important contributions to this study, whether it be in the ideation, research design, implementation, collection of data, analysis of data, interpretation of results, or all of these domains. All authors participated in the process of drafting, editing, or critically evaluating the manuscript; provided their official approval of the version to be published; reached a consensus on the journal to which the manuscript was submitted; and consented to be responsible for all parts of the work.