Background: Chronic obstructive pulmonary disease (COPD) is a major and increasing global health problem that results in progressive airway obstruction. Cigarette smoke (CS) exposure, a major cause for COPD, induces mitochondrial damage, which has been implicated in sarcopenia pathogenesis. The current study sought to examine the involvement of ABHD2 in the mechanisms of development of COPD-related sarcopenia. Methods: The involvement of ABHD2 was examined using in vivo CS-exposure model using ABHD2-KO mice. In CSE-induced COPD mouse models, ROS production and inflammation were measured using fluorescent probes and Western blot analysis. Results: Increased ROS was responsible for myotube atrophy by activating Muscle Ring Finger 1 and inhibiting Myod. ABHD2-KO mice with prolonged CS exposure showed enhanced muscle atrophy. Conclusion: These results indicated that ABHD2 played a key protective role in COPD-related skeletal muscle atrophy through a three-dimensional interactive network coordinating angiogenesis, oxidative stress defense, and inflammatory microenvironment regulation.

Background: Chronic obstructive pulmonary disease (COPD) ranks as the third leading cause of death worldwide and is primarily caused by cigarette smoke (CS) exposure. A reduction in the number of ciliated cells significantly contributes to the development and progression of COPD. Nicastrin (NCSTN), a core subunit of γ-secretase, plays an important role in the pathogenesis of various tumors. However, to date, no studies have demonstrated its role in COPD. The aim of this study was to investigate the effect and underlying mechanism of NCSTN on the differentiation of airway epithelial basal cells into ciliated cells under cigarette smoke extract (CSE) exposure. Methods: Mouse tracheal epithelial basal cells were differentiated at the air-liquid interface (ALI) in vitro and exposed to CSE for 7 days. Lentiviral overexpression and knockdown of NCSTN in basal cells were performed. The effects on cell differentiation, NCSTN expression and the Notch signaling pathway in response to CSE were assessed using reverse transcription‑quantitative PCR (RT-qPCR) and western blotting (WB). Results: We found that CSE exposure in vitro inhibited ciliated cell differentiation, while simultaneously increasing the expression of NCSTN, Notch3, and Hes1. Overexpression of NCSTN suppressed ciliated cell differentiation and induced Notch3 activation. Conversely, knockdown of NCSTN attenuated the CSE-mediated reduction in ciliated cell differentiation and inhibited Notch3 activation. Our findings indicate that CSE exposure inhibits basal cell differentiation into ciliated cells by upregulating the NCSTN-Notch3-Hes1 pathway. Conclusions: Inhibition of the NCSTN-Notch3-Hes1 pathway promoted ciliated cell differentiation and ameliorated the CSE-induced reduction in ciliated cells.

Cuproptosis, a recently identified form of regulated cell death, relies on accumulated copper (Cu) ions and a disrupted mitochondrial respiratory chain. The role of cuproptosis in various diseases, especially respiratory diseases of pulmonary fibrosis, chronic obstructive pulmonary disease, and lung cancer, has been increasingly recognized. This article reviews the dysregulation of Cu homeostasis, cuproptosis's molecular mechanisms, and recent research developments in respiratory diseases, while also exploring potential therapeutic targets and clinical applications.

Objective: Asthma development is significantly influenced by the abnormal proliferation and migration of human airway smooth muscle cells (HASMCs). The aim of this study was to investigate the role and molecular mechanisms of the m6A methyltransferase METTL3 in platelet-derived growth factor BB (PDGF-BB)-treated HASMCs. Methods: An in vitro model of HASMCs stimulation was constructed by PDGF-BB. Proliferation, migration, and levels of inflammatory factors of HASMCs were detected by CCK-8, Transwell assay, and ELISA, respectively. m6A modification sites in GAS5 were predicted using WHISTLE. m6A methylation level in GAS5 was detected by MeRIP-qPCR. The RNA stability of GAS5 was assessed by RNA decay assay. Targeted binding sites between miR-29c-3p and GAS5 or VAMP2 were predicted using starBase, and their targeting relationship was verified by dual-luciferase reporter assay. Results: METTL3 levels were decreased in PDGF-BB-induced HASMCs. Enhancing METTL3 expression in HASMCs inhibited PDGF-BB-induced proliferation, migration, and inflammation. METTL3-mediated m6A methylation decreased GAS5 stability, thereby inhibiting GAS5 expression. GAS5 targeted miR-29c-3p and regulated VAMP2 expression. In PDGF-BB-treated HASMCs, enhancing VAMP2 mitigated the effect of METTL3 upregulation. Conclusion: METTL3 inhibits HASMC proliferation, migration, and inflammation in asthma by regulating the GAS5/miR-29c-3p/VAMP2 axis.