Mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury by Kun Peng instant download

Mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury by Kun Peng instant download

ABSTRACT Keywords: An earlier study found that respiratory cadmium chloride (CdCl2) exposure caused COPD-like lung injury. This Chronic obstructive pulmonary disease study aimed to explore whether mitochondrial dysfunction-mediated alveolar epithelial senescence is involved in Cadmium chloride CdCl2-induced COPD-like lung injury. Adult C57BL/6 mice were exposed to CdCl2 (10 mg/L) aerosol for six Mitochondrial dysfunction months. Beta-galactosidase-positive cells, p21 and p16 were increased in CdCl2-exposed mouse lungs. The in Cellular senescence vitro experiments showed that γ-H2AX 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 * Correspondence to: Department of Toxicology, School of Public Health, Anhui Medical University, Hefei 230032, China. ** Correspondence to: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China. E-mail addresses: [email protected] (D.-X. Xu), [email protected] (Z.-X. Tan).