Mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl 2 -induced COPD-like lung injury.

Autor: Peng K; Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Anhui Medical University, Hefei, China., Yao YX; Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Anhui Medical University, Hefei, China., Lu X; Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China., Wang WJ; Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Anhui Medical University, Hefei, China., Zhang YH; Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China., Zhao H; Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Anhui Medical University, Hefei, China., Wang H; Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China., Xu DX; Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China. Electronic address: xudex@126.com., Tan ZX; Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: tanzhuxia@126.com.
Jazyk: angličtina
Zdroj: Journal of hazardous materials [J Hazard Mater] 2024 Sep 05; Vol. 476, pp. 135103. Date of Electronic Publication: 2024 Jul 04.
DOI: 10.1016/j.jhazmat.2024.135103
Abstrakt: 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 CdCl 2 -induced COPD-like lung injury. Adult C57BL/6 mice were exposed to CdCl 2 (10 mg/L) aerosol for six months. Beta-galactosidase-positive cells, p21 and p16 were increased in CdCl 2 -exposed mouse lungs. The in vitro experiments showed that γ-H 2 AX was elevated in CdCl 2 -exposed alveolar epithelial cells. The cGAS-STING pathway was activated in CdCl 2 -exposed alveolar epithelial cells and mouse lungs. Cxcl1, Cxcl9, Il-10, Il-1β and Mmp2, several senescence-associated secretory phenotypes (SASP), were upregulated in CdCl 2 -exposed alveolar epithelial cells. Mechanistically, CdCl 2 exposure caused SIRT3 reduction and mitochondrial dysfunction in mouse lungs and alveolar epithelial cells. The in vitro experiment found that Sirt3 overexpression attenuated CdCl 2 -induced alveolar epithelial senescence and SASP. The in vivo experiments showed that Sirt3 gene knockout exacerbated CdCl 2 -induced alveolar epithelial senescence, alveolar structure damage, airway inflammation and pulmonary function decline. NMN, an NAD + precursor, attenuated CdCl 2 -induced alveolar epithelial senescence and SASP in mouse lungs. Moreover, NMN supplementation prevented CdCl 2 -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 CdCl 2 -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.)
Databáze: MEDLINE
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