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Identification of Lipocalin 2 as a Potential Ferroptosis-related Gene in Ulcerative Colitis

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机构： [1]The First Clinical College, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China. [2]Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Chinese Medicine, Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing, China100000. [3]The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, China524023. [4]Experimental Animal Center, Guangdong Medical University, Zhanjiang, Guangdong, China524023. [5]The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, Guangdong, China524023.

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关键词： ferroptosis ulcerative colitis lipocalin 2 lipid peroxidation machine learning

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Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease generally limited to the mucosa and submucosa of the colon. Recent studies suggest that ferroptosis is a novel programmed cell death that may be involved in the process of UC. However, the mechanism of ferroptosis in UC remains to be further investigated.The genes associated with UC and ferroptosis were screened by bioinformatics methods, and a random forest model was constructed to identify the core genes of UC and validated with external data sets. Establishment of dextran sodium sulfate (DSS) induced UC in an animal model in vivo. Interferon (IFN)-γ primed immortalized bone marrow-derived macrophages cells stimulated with Lipopolysaccharides (LPS) inflammation model and LPS-stimulated Caco-2 cells colitis model in vitro were constructed. The potential link between Lipocalin-2 (LCN2) and UC ferroptosis was explored by flow cytometry, Fe2+ assay, Western Blot, gene knockdown, hematoxylin and eosin staining, and immunohistochemistry staining.Analysis of differentially expressed genes (DEGs) showed that LCN2 was highly expressed in UC. The protein-protein interaction (PPI) networks showed that ferroptosis-associated DEGs were highly correlated with the immune gene LCN2. The most important gene in the random forest model, LCN2, was identified as a core gene in UC. In the LPS/IFN-γ-induced inflammation model, LCN2 expression was elevated, lipid peroxidation, Fe2+, ACSL4 and COX-2 levels increased, whereas GPX4 and FTH1 expression decreased. Similarly, in the DSS-induced UC mouse model, Occludin, ZO-1, Claudin-1, and GPX4 expression were significantly decreased, but ACSL4 and LCN2 expression were elevated. In addition, the use of Ferrostatin-1 (Fer-1) can significantly reverse its trend. More importantly, silencing of LCN2 suppressed ferroptosis events in both the LPS/IFN-γ-induced inflammation model and the LPS-stimulated colitis model.In conclusion, our study demonstrates that LCN2 is a key factor in the regulation of ferroptosis in UC and provides additional evidence for the important role of ferroptosis in UC.© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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出版当年[2022]版：

大类 | 2 区医学

小类 | 3 区胃肠肝病学

最新[2025]版：

大类 | 3 区医学

小类 | 3 区胃肠肝病学

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第一作者机构： [1]The First Clinical College, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China.

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通讯机构： [3]The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, China524023. [5]The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, Guangdong, China524023. [*1]No. 2 Wenming East Road, Xiashan District, Zhanjiang City, Guangdong Province, China

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Identification of Lipocalin 2 as a Potential Ferroptosis-related Gene in Ulcerative Colitis

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