The deubiquitinase USP2 preserves intestinal barrier through the TRAF6/ NF-κB/MLCK/MLC signaling in ulcerative colitis
文献类型：期刊论文
| 作者 | Zhou, Ruochen4,5,6; Cui, Yuanyuan5,6; Wang, Weihao3,6; Qu, Yidan2,6; Zhang, Gaojie1,6; Wang, Xue6; Sun, Yili5,6; Li, Jia3,4,5,6
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| 刊名 | INTERNATIONAL IMMUNOPHARMACOLOGY
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| 出版日期 | 2025-09-23 |
| 卷号 | 162页码:12 |
| 关键词 | Ubiquitin-specific protease 2 Ulcerative colitis Intestinal epithelial cell Tight junction |
| ISSN号 | 1567-5769 |
| DOI | 10.1016/j.intimp.2025.115099 |
| 英文摘要 | Disruption of the physical barrier of intestinal epithelial cells is a hallmark of ulcerative colitis (UC). Deubiquitinating enzymes (DUBs), which modify the stability, localization, or activity of substrates by removing ubiquitin chains, have been involved in the development of UC. However, the biological role of DUBs in intestinal epithelial cells (IECs) has yet to be extensively investigated. In this work, we revealed that USP2 as the most differentially expressed DUB in the colon of mice with dextran sodium sulfate (DSS)-induced colitis and was downregulated mainly in the intestinal epithelium. Notably, the expression of USP2 was correlated with the levels of tight junction (TJ) proteins. Furthermore we showed that USP2 expression was reduced in the intestine of mice with acute colitis induced by DSS, as well as in IECs stimulated with LPS. Overexpression of USP2 restored the LPS-induced the reduction of TJPs. Mechanistically, USP2 attenuates the activation of NF-kappa B and the phosphorylation of the myosin light chain, possibly by reducing the K63-linked polyubiquitin chain on the tumour necrosis factor receptor-associated factor 6 (TRAF6). In vivo, colonic-specific overexpression of USP2 in mice ameliorated DSS-induced barrier damage. Together, our study proposed USP2 as a new deubiquitinating enzyme molecule involved in the course of UC regulating the function of IECs during the progression of UC. |
| WOS关键词 | MODULATION |
| 资助项目 | Key R&D Program of Shandong Province, China[2024CXPT028] ; National Natural Science Foundation of Shandong Province, China[ZR2024QC286] ; National Natural Science Foundation of Shanghai Province, China[24ZR1477400] ; Taishan Scholar Foundation of Shandong Province[tstp0648] ; National Natural Science Foundation of China[81903682] |
| WOS研究方向 | Immunology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001517071900001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318666]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Sun, Yili; Li, Jia |
| 作者单位 | 1.Henan Univ, Coll Pharm, Kaifeng 475004, Peoples R China 2.Shandong First Med Univ & Shandong Acad Med Sci, Jinan 264000, Shandong, Peoples R China 3.Shandong Second Med Univ, Sch Pharm, Weifang 261053, Shandong, Peoples R China 4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 6.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhou, Ruochen,Cui, Yuanyuan,Wang, Weihao,et al. The deubiquitinase USP2 preserves intestinal barrier through the TRAF6/ NF-κB/MLCK/MLC signaling in ulcerative colitis[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2025,162:12. |
| APA | Zhou, Ruochen.,Cui, Yuanyuan.,Wang, Weihao.,Qu, Yidan.,Zhang, Gaojie.,...&Li, Jia.(2025).The deubiquitinase USP2 preserves intestinal barrier through the TRAF6/ NF-κB/MLCK/MLC signaling in ulcerative colitis.INTERNATIONAL IMMUNOPHARMACOLOGY,162,12. |
| MLA | Zhou, Ruochen,et al."The deubiquitinase USP2 preserves intestinal barrier through the TRAF6/ NF-κB/MLCK/MLC signaling in ulcerative colitis".INTERNATIONAL IMMUNOPHARMACOLOGY 162(2025):12. |
入库方式： OAI收割
来源：上海药物研究所
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