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

β2-microglobulin (β2m) is the light-chain subunit of major histocompatibility complex class I (MHC I) molecules. Our group previously showed that β2m contributes to emphysema development by inducing epithelial cell senescence. However, the mechanism linking β2m 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 β2m is associated with mitochondrial dysfunction and a senescent phenotype.

Human bronchial epithelial BEAS-2B cells were exposed in vitro for 48 hours to recombinant human β2m 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.

β2m and CSE increased SA-β-gal staining in BEAS-2B cells, indicating enhanced cellular senescence. β2m and CSE also decreased MMP, increased ROS and mtROS levels, and reduced OCR, indicating mitochondrial dysfunction. In addition, β2m and CSE reduced BEAS-2B cell proliferation and increased apoptosis.

β2m 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 β2m may contribute to epithelial aging in COPD/emphysema, although further mechanistic investigation and in vivo validation are required.