Abstract
Cigarette smoke (CS), a main source of indoor air pollution, is a primary risk factor for emphysema, and aberrant cellular autophagy is related to the pathogenesis of emphysema. Circular RNAs (circRNAs) affect the expression of mRNAs via acting as microRNA (miRNA) sponges, but their role in emphysema progression is not established. In the present investigation, CS, acting on alveolar epithelial cells, caused higher levels of miR-21, p-ERK, and cleaved-caspase 3 and led to lower levels of circRNA_0026344 and PTEN, which induced autophagy and apoptosis. miR-21 suppressed the expression of PTEN, which was involved in the regulation of autophagy and apoptosis. Further, in alveolar epithelial cells, overexpression of circRNA_0026344 blocked cigarette smoke extract (CSE)–induced autophagy and apoptosis, but this blockage was reversed by upregulation of miR-21 with a mimic. These results demonstrated that, in alveolar epithelial cells, CS decreases circRNA_0026344 levels, which sponge miR-21 to inhibit the miR-21 target, PTEN, which, in turn, activates ERK and thereby promotes autophagy and apoptosis, leading to emphysema. Thus, for emphysema, circRNA_0026344 regulates the PTEN/ERK axis by sponging miR-21, which is associated with the CS-induced autophagy and apoptosis of alveolar epithelial cells. In sum, the present investigation identifies a novel mechanism for CS-induced emphysema and provides information useful for the diagnosis and treatment of CS-induced emphysema.
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The authors thank Donald L. Hill (University of Alabama at Birmingham, USA), an experienced, English-speaking scientific editor, for editing.
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This work was supported by the Natural Science Foundations of China (81973085, 81803276, 81973005), the Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (BJ2020006), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (2019).
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Jing Zhao and Haibo Xia designed and wrote the manuscript; Jing Zhao, Haibo Xia, and Yan Wu performed in vivo experiments; Jing Zhao and Haibo Xia performed in vitro experiments; Lu Lu, Jing Sun, and Cheng Cheng analyzed the data; Tao Bian and Qizhan Liu assisted with the manuscript revision; Quanyong Xiang and Qizhan Liu supervised the study.
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All human samples procedures were approved by the Ethics Committee of Wuxi People’s Hospital affiliated with Nanjing Medical University. All animal procedures were reviewed and approved by the Institutional Animal Care and Use Committee at Nanjing Medical University.
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Highlights
1. In alveolar epithelial cells, CS lowers levels of circRNA_0026344 in a concentration-dependent manner.
2. CS causes autophagy and apoptosis of alveolar epithelial cells.
3. CircRNA_0026344 mediates autophagy and apoptosis in CS-induced emphysema.
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Zhao, J., Xia, H., Wu, Y. et al. CircRNA_0026344 via miR-21 is involved in cigarette smoke–induced autophagy and apoptosis of alveolar epithelial cells in emphysema. Cell Biol Toxicol 39, 929–944 (2023). https://doi.org/10.1007/s10565-021-09654-5
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DOI: https://doi.org/10.1007/s10565-021-09654-5