1. Mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl 2 -induced COPD-like lung injury.
- Author
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Peng K, Yao YX, Lu X, Wang WJ, Zhang YH, Zhao H, Wang H, Xu DX, and Tan ZX
- Subjects
- Animals, Alveolar Epithelial Cells drug effects, Alveolar Epithelial Cells metabolism, Male, Lung Injury chemically induced, Lung Injury pathology, Sirtuin 3 metabolism, Sirtuin 3 genetics, Mice, Mice, Knockout, Mice, Inbred C57BL, Mitochondria drug effects, Mitochondria metabolism, Cellular Senescence drug effects, Pulmonary Disease, Chronic Obstructive pathology, Pulmonary Disease, Chronic Obstructive chemically induced, Pulmonary Disease, Chronic Obstructive metabolism
- Abstract
An earlier study found that respiratory cadmium chloride (CdCl
2 ) exposure caused COPD-like lung injury. This study aimed to explore whether mitochondrial dysfunction-mediated alveolar epithelial senescence is involved in CdCl2 -induced COPD-like lung injury. Adult C57BL/6 mice were exposed to CdCl2 (10 mg/L) aerosol for six months. Beta-galactosidase-positive cells, p21 and p16 were increased in CdCl2 -exposed mouse lungs. The in vitro experiments showed that γ-H2 AX was elevated in CdCl2 -exposed alveolar epithelial cells. The cGAS-STING pathway was activated in CdCl2 -exposed alveolar epithelial cells and mouse lungs. Cxcl1, Cxcl9, Il-10, Il-1β and Mmp2, several senescence-associated secretory phenotypes (SASP), were upregulated in CdCl2 -exposed alveolar epithelial cells. Mechanistically, CdCl2 exposure caused SIRT3 reduction and mitochondrial dysfunction in mouse lungs and alveolar epithelial cells. The in vitro experiment found that Sirt3 overexpression attenuated CdCl2 -induced alveolar epithelial senescence and SASP. The in vivo experiments showed that Sirt3 gene knockout exacerbated CdCl2 -induced alveolar epithelial senescence, alveolar structure damage, airway inflammation and pulmonary function decline. NMN, an NAD+ precursor, attenuated CdCl2 -induced alveolar epithelial senescence and SASP in mouse lungs. Moreover, NMN supplementation prevented CdCl2 -induced COPD-like alveolar structure damage, epithelial-mesenchymal transition and pulmonary function decline. These results suggest that mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2 -induced COPD-like lung injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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