Cigarette smoke-induced apoptosis via regulation of the miR-122/PTEN/AKT axis in NR8383 cells and rat model of COPD.

Abstract

BACKGROUND: PM2.5-induced COPD lacks effective therapies due to unclear pathogenesis. This study explores the role of miR-122 and PTEN in PM2.5-related COPD. METHODS: Using a combination ofandassays, including cigarette smoke extract (CSE)-induced NR8383 cells and a rat smoke model, combined with MTT, qPCR, flow cytometry, WB, HE staining, Masson staining, HIC, and TUNEL assays, we investigated the role of microRNA-122 (miR-122) and phosphatase and tensin homolog (PTEN) in the molecular mechanisms underlying PM2.5-induced COPD. RESULTS: Our findings demonstrate that CSE-induced the down-regulated expression of miR-122 leads to the activation of PTEN, which in turn regulates the AKT signaling pathway in NR8383 cells. This modulation results in decreased expression of B-cell lymphoma 2 (BCL2), promoting cell apoptosis. Besides, the result from a rat model of COPD exposed to smoke also confirms this molecular axis which ultimately exacerbating COPD. Specifically, compared with the control, there is significant pulmonary structural damage in model rats exposed to PM2.5, including enlarged alveolar intervals, increased alveolar cavity size, pulmonary fibrosis, and evidence of alveolar destruction with concomitant parabronchial inflammation. CONCLUSION: Our research reveals novel insights of PM2.5-induced COPD and proposes the miR-122/PTEN pathway as a potential therapeutic target.