IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Molecular medicine reports Pub Date : 2025-04-01 Epub Date: 2025-02-28 DOI:10.3892/mmr.2025.13473
Xu Zhou, Xingyou Zhao, Yanning Li, Baoqing Zhang
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引用次数: 0

摘要

闭塞性支气管炎(Bronchiolitis obliterans,BO)是一种破坏性肺纤维化疾病,2,3-丁二酮(又称双乙酰(DA))可诱发部分BO;然而,DA对BO的影响机制尚不清楚。本研究利用经 DA 处理或未经 DA 处理的大鼠肺组织进行了生物信息学分析,结果发现 DA 组样本中细胞增殖调节蛋白磷酸酶 2A 抑制剂(CIP2A)显著增加。CIP2A与炎症和上皮-间质转化(EMT)有关,并促进肺损伤;然而,它对DA诱导的BO的影响及其潜在机制仍不清楚。为了解决这些问题,我们在大鼠和细胞中建立了DA处理的BO模型,并施用乙氧胰鸟苷(一种CIP2A抑制剂)来诱导CIP2A的减少。病理变化通过苏木精、伊红、Masson 和 Giemsa 染色法检测。逆转录-定量 PCR、Western 印迹、免疫组织化学、免疫荧光和酶联免疫吸附试验被用来检测 CIP2A 的表达和病理相关标记物的水平。值得注意的是,抑制 CIP2A 能改善 BO 的病理特征,包括减少管腔内闭塞、炎症浸润和纤维化。在抑制了CIP2A的样本中,炎症、纤维化和EMT标记物的表达也有所下降。此外,研究还发现 CIP2A 抑制剂是通过核因子-κB(NF-κB)途径发挥作用的;NF-κB 抑制剂 α 的磷酸化和 p65 的核转位均有所减少。总之,这些结果表明,CIP2A 可通过激活 NF-κB 信号通路,增加炎症、纤维化和 EMT,从而促进 BO 的发展。因此,抑制 CIP2A 可被视为治疗 BO 的一种潜在策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CIP2A promotes bronchiolitis obliterans by activating the NF‑κB pathway.

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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来源期刊
Molecular medicine reports
Molecular medicine reports 医学-病理学
CiteScore
7.60
自引率
0.00%
发文量
321
审稿时长
1.5 months
期刊介绍: Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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