β2-Microglobulin Induces Mitochondrial Dysfunction Accompanied by Bronchial Epithelial Cell Senescence

Purpose: β 2-microglobulin (β 2m) is the light-chain subunit of major histocompatibility complex class I (MHC I) molecules. Our group previously showed that β 2m contributes to emphysema development by inducing epithelial cell senescence. However, the mechanism linking β 2m to epithelial senescence remains unclear. Previous studies have reported mitochondrial dysfunction in senescent lung cells from patients with emphysema, suggesting a potential mechanistic pathway. This in vitro study used BEAS-2B human bronchial epithelial cells to evaluate whether exposure to β 2m is associated with mitochondrial dysfunction and a senescent phenotype. Methods: Human bronchial epithelial BEAS-2B cells were exposed in vitro for 48 hours to recombinant human β 2m or cigarette smoke extract (CSE). Cellular senescence was assessed by senescence-associated β-galactosidase (SA-β-gal) staining. Mitochondrial dysfunction was evaluated by measuring mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial ROS (mtROS), oxygen consumption rate (OCR), and real-time adenosine triphosphate (ATP) production rate. Cell proliferation and apoptosis were assessed using CCK-8 and Annexin V-FITC/PI assays, respectively. Results: β 2m and CSE increased SA-β-gal staining in BEAS-2B cells, indicating enhanced cellular senescence. β 2m and CSE also decreased MMP, increased ROS and mtROS levels, and reduced OCR, indicating mitochondrial dysfunction. In addition, β 2m and CSE reduced BEAS-2B cell proliferation and increased apoptosis. Conclusion: β 2m exposure was associated with mitochondrial dysfunction and a senescent phenotype in BEAS-2B cells, accompanied by reduced proliferation and increased apoptosis. These findings suggest that β 2m may contribute to epithelial aging in COPD/emphysema, although further mechanistic investigation and in vivo validation are required.