Role of HSPA2 in CSE-Induced Apoptosis of BEAS-2B Cells

<bold>Background:</bold> Chronic obstructive pulmonary disease (COPD) poses significant global health challenges, primarily linked to smoking-induced lung damage. Despite extensive research, the involvement of epigenetic factors, notably HSPA2, remains poorly understood in COPD. <bold>Objective:</bold> This study investigates HSPA2's role in cigarette smoke extract (CSE)-induced apoptosis of BEAS-2B cells, aiming to elucidate its potential contribution to COPD pathogenesis. <bold>Methods:</bold> Whole-genome methylation sequencing was performed on PBMCs from 8 COPD patients and 8 healthy controls. RT-qPCR was conducted on samples from 62 COPD patients and 80 healthy controls. Lentivirus-mediated HSPA2 overexpression in BEAS-2B cells was followed by CSE exposure. RT-qPCR, TUNEL assay, flow cytometry, and Western blot assessed gene expression, apoptosis, and signaling pathways. <bold>Results:</bold> Methylation sequencing revealed hypermethylation-associated HSPA2 downregulation in COPD. RT-qPCR and immunohistochemistry validated this. CSE exposure significantly reduced HSPA2 expression in BEAS-2B cells. Lentivirus-mediated HSPA2 overexpression followed by CSE exposure attenuated HSPA2 expression and induced apoptosis of BEAS-2B cells. Further analyses demonstrated activation of the Erk1/2 pathway in response to CSE-induced HSPA2 downregulation <bold>Conclusion:</bold> Hypermethylation-associated HSPA2 downregulation contributes to CSE-induced apoptosis in BEAS-2B cells, implicating its role in COPD pathogenesis. HSPA2 presents a potential therapeutic target for COPD management.