CIP2A promotes bronchiolitis obliterans by activating the NF‑&kappa;B pathway

Zhou,Xu; Zhao,Xingyou; Li,Yanning; Zhang,Baoqing

doi:10.3892/mmr.2025.13473

CIP2A promotes bronchiolitis obliterans by activating the NF‑κB pathway

Authors:
- Xu Zhou
- Xingyou Zhao
- Yanning Li
- Baoqing Zhang
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Affiliations: Department of Pediatrics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250011, P.R. China, The First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China
Published online on: February 24, 2025 https://doi.org/10.3892/mmr.2025.13473
Article Number: 108
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bronchiolitis obliterans (BO) is a destructive fibrotic lung disease, which can be partly induced by 2,3‑butanedione [also known as diacetyl (DA)]; however, the mechanism underlying the effects of DA on BO is not clear. In the present study, a bioinformatics analysis was performed using DA‑treated or untreated lung tissues of rats, and it was observed that cell proliferation regulating inhibitor of protein phosphatase 2A (CIP2A) was significantly increased in samples from the DA group. CIP2A is associated with inflammation and epithelial‑mesenchymal transition (EMT), and facilitates lung injury; however, its effect on DA‑induced BO and the underlying mechanism remain unknown. To solve these issues, DA‑treated models of BO were established in rats and cells, and ethoxysanguinarine (a CIP2A inhibitor) was administered to induce a decrease in CIP2A. The pathological changes were detected by hematoxylin and eosin, Masson and Giemsa staining. Reverse transcription‑quantitative PCR, western blotting, immunohistochemistry, immunofluorescence and enzyme‑linked immunosorbent assay were used to measure CIP2A expression and levels of pathology‑related markers. Notably, inhibition of CIP2A ameliorated the pathological features of BO, including reduced intraluminal occlusion, inflammatory infiltration and fibrosis. The expression of inflammation, fibrosis and EMT markers was also decreased in samples with CIP2A inhibition. Furthermore, CIP2A inhibition was revealed to work through the nuclear factor‑κB (NF‑κB) pathway; phosphorylation of NF‑κB inhibitor α and nuclear translocation of p65 were reduced. In summary, these results demonstrated that CIP2A may promote BO development by increasing inflammation, fibrosis and EMT through activating the NF‑κB signaling pathway. Therefore, inhibition of CIP2A may be considered a potential strategy for BO treatment.

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