Progesterone (P4) ameliorates cigarette smoke-induced chronic obstructive pulmonary disease (COPD)

• Published in: Molecular medicine (Cambridge, Mass.) Vol. 30; no. 1; pp. 123 - 16
• Main Authors: Xie, Bin, Chen, Qiong, Dai, Ziyu, Jiang, Chen, Chen, Xi
• Format: Journal Article
• Language: English
• Published: England BioMed Central 13.08.2024; BMC
• Subjects: Airway epithelium; Animals; Apoptosis - drug effects; Cell growth; Cell Line; Cell Proliferation - drug effects; Chronic obstructive pulmonary disease; Chronic obstructive pulmonary disease (COPD); Cigarette Smoking - adverse effects; Cigarettes; Disease Models, Animal; Humans; Hydrogen Peroxide - metabolism; Laboratory animals; Lungs; Male; Membrane Potential, Mitochondrial - drug effects; Mice; Mice, Inbred C57BL; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial DNA; Mitochondrial dysfunction; Oxidative injury; Oxidative stress; Oxidative Stress - drug effects; Pathogenesis; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; Phosphorylation; Progesterone (P4); Progesterone - pharmacology; Proteins; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - etiology; Pulmonary Disease, Chronic Obstructive - metabolism; Reactive Oxygen Species - metabolism; Signal transduction; Signal Transduction - drug effects; Sirtuin 1 - metabolism; Smoke - adverse effects; Smooth muscle; United States > US; China; Shanghai China; Chronic obstructive pulmonary disease (COPD); Mitochondrial dysfunction; Airway epithelium; Progesterone (P4); Oxidative injury
• ISSN: 1528-3658; 1076-1551; 1528-3658
• DOI: 10.1186/s10020-024-00883-y

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with high morbidity and mortality worldwide. Oxidative injury and mitochondrial dysfunction in the airway epithelium are major events in COPD progression. The therapeutic effects of Progesterone (P4) were investigated in vivo and in vitro in this study. In vivo, in a cigarette smoke (CS) exposure-induced COPD mouse model, P4 treatment significantly ameliorated CS exposure-induced physiological and pathological characteristics, including inflammatory cell infiltration and oxidative injury, in a dose-dependent manner. The c-MYC/SIRT1/PGC-1α pathway is involved in the protective function of P4 against CS-induced COPD. In vitro, P4 co-treatment significantly ameliorated H O -induced oxidative injury and mitochondrial dysfunctions by promoting cell proliferation, increasing mitochondrial membrane potential, decreasing ROS levels and apoptosis, and increasing ATP content. Moreover, P4 co-treatment partially attenuated H O -caused inhibition in Nrf1, Tfam, Mfn1, PGR-B, c-MYC, SIRT1, and PGC-1α levels. In BEAS-2B and ASM cells, the c-MYC/SIRT1 axis regulated P4's protective effects against H O -induced oxidative injury and mitochondrial dysfunctions. P4 activates the c-MYC/SIRT1 axis, ameliorating CS-induced COPD and protecting both airway epithelial cells and smooth muscle cells against H O -induced oxidative damage. PGC-1α and downstream mitochondrial signaling pathways might be involved.