E3泛素连接酶RNF138抑制溃疡性结肠炎的发生及进展

doi:10.16352/j.issn.1001-6325.2023.06.0941

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (6): 941-947.doi: 10.16352/j.issn.1001-6325.2023.06.0941

E3泛素连接酶RNF138抑制溃疡性结肠炎的发生及进展

邓博雅¹, 路亚岚², 羽思³, 张旖垚¹, 黄婧怡³, 李玥^3*, 刘长征^1*

1.中国医学科学院基础医学研究所北京协和医学院基础学院生物化学与分子生物学系医学分子生物学国家重点实验室, 北京 100005;
2.中国医学科学院北京协和医学院医学实验动物研究所国家卫生健康委员会人类比较医学重点实验室,北京 100021;
3.中国医学科学院北京协和医学院北京协和医院消化内科,北京 100730

收稿日期:2023-03-06 修回日期:2023-04-18 出版日期:2023-06-05 发布日期:2023-05-31
通讯作者: ^*cz-liu@ibms.pumc.edu.cn;liyue@pumch.cn
基金资助:
中国医学科学院医学与健康科技创新工程(2022-I2M-JB-003)

E3 ubiquitinase RNF138 inhibits the development of ulcerative colitis

DENG Boya¹, LU Yalan², YU Si³, ZHANG Yiyao¹, HUANG Jingyi³, LI Yue^3*, LIU Changzheng^1*

1. State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005;
2. Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Human Disease Comparative Medicine, National Health Commission, Beijing 100021;
3. Department of Gastroenterology, Peking Union Medical College Hospital, CAMS ＆ PUMC, Beijing 100730, China

Received:2023-03-06 Revised:2023-04-18 Online:2023-06-05 Published:2023-05-31
Contact: ^*cz-liu@ibms.pumc.edu.cn;liyue@pumch.cn

摘要/Abstract

摘要： 目的研究E3泛素连接酶RNF138在溃疡性结肠炎(UC)中的作用。方法利用GEO数据库分析活动期、缓解期以及经免疫抑制剂治疗后UC样本中RNF138的表达水平;利用RNF138基因敲除小鼠构建UC模型,对模型小鼠进行病理学观察及组织学分析;取小鼠结肠组织进行转录组测序,初步探究RNF138敲除促进UC进展的可能机制;利用免疫组化和Western blot检测小鼠结肠组织中RNF138和phospho-NF-κB p65(p-p65)的表达水平;通过qPCR实验检测核因子NF-кB通路靶基因的表达水平;利用免疫组化对临床样本中RNF138和p-p65的表达进行检测。结果 GEO数据库及临床样本分析显示,与缓解期相比,活动期UC组织中RNF138表达下调(P＜0.05);敲除RNF138促进DSS诱导的UC发生及进展(P＜0.05);敲除RNF138促进p-p65及其靶基因表达 (P＜0.05),提示NF-кB信号通路激活。结论 RNF138通过阻断NF-кB通路活化抑制UC发生及进展。

关键词: RNF138, 溃疡性结肠炎, NF-кB

Abstract: Objective To explore the role of RNF138 (ring finger protein 138) in the ulcerative colitis (UC). Methods The expression of RNF138 in active, remission and ulcerative colitis upon immunosuppressive treatment was analyzed by GEO database. The UC model was constructed by RNF138-deficient mice. The pathological observation, histological analysis and colon measurement were performed by the model mice. The transcriptome analysis was employed by using mouse colon tissue samples. The expression levels of RNF138 and p-p65 in colon tissue of model mice were detected by immunohistochemistry and Western blots. The expression of target gene of NF-кB pathway was detected by qPCR. Immunohistochemistry was used to evaluate the expression of RNF138 and NF-кB p65 in clinical samples of UC. Results GEO database and clinical samples showed that the expression of RNF138 decreased in the samples of active UC as compared to that in the remission stage(P＜0.05). Knocking out RNF138 promoted the occurrence and progression of DSS induced UC (P＜0.05). Knocking out RNF138 promoted upregulation of p-p65 and its target gene expression(P＜0.05), indicating NF-кB signal pathway activation. Conclusions RNF138 inhibits the development of UC through suppressing the NF-кB genetic pathway.

Key words: RNF138, ulcerative colitis, NF-кB

中图分类号:

R574

邓博雅, 路亚岚, 羽思, 张旖垚, 黄婧怡, 李玥, 刘长征. E3泛素连接酶RNF138抑制溃疡性结肠炎的发生及进展[J]. 基础医学与临床, 2023, 43(6): 941-947.

DENG Boya, LU Yalan, YU Si, ZHANG Yiyao, HUANG Jingyi, LI Yue, LIU Changzheng. E3 ubiquitinase RNF138 inhibits the development of ulcerative colitis[J]. Basic & Clinical Medicine, 2023, 43(6): 941-947.

参考文献 8

[1]	Kucharzik T, Koletzko S, Kannengiesser K, et al. Ulcera-tive Colitis-Diagnostic and Therapeutic Algorithms[J]. Dtsch Arztebl Int, 2020, 117:564-574.
[2]	Porter RJ, Kalla R, Ho GT. Ulcerative colitis: recent advances in the understanding of disease pathogenesis[J]. F1000Res, 2020, 9:F1000 Faculty Rev-294.doi:10.12688/f1000research.20805.1.
[3]	Yu Z, Quan YN, Huang ZQ, et al. Monitoring oxidative stress, immune response, Nrf2/NF-κB signaling molecules of Rhynchocypris lagowski living in BFT system and exposed to waterborne ammonia[J]. Ecotoxicol Environ Saf, 2020, 205:111161.doi:10.1016/jecoenv.2020.111161.
[4]	Lu Y, Huang R, Ying J, et al. RING finger 138 deregulation distorts NF-кB signaling and facilities colitis switch to aggressive malignancy[J]. Signal Transduct Target Ther, 2022, 7:185.doi:10.1038/s41392-022-00985-1.
[5]	Wu H, Li X, Feng M, et al. Downregulation of RNF138 inhibits cellular proliferation, migration,invasion and EMT in glioma cells via suppression of the Erk signaling pathway.[J]Oncol ep, 2018, 40:3285-3296.
[6]	Zhou YX, Chen SS, Wu TF, et al. A novel gene RNF138 expressed in human gliomas and its function in the glioma cell line U251[J]. Anal, Cell, 2012, 35:167-178.
[7]	Peng X, Zheng X, Liao M, et al. TRAF6 autophagic degradation by avibirnavirus VP3 inhibits antiviral innate immunity via blocking NFKB/NF-κB activation[J]. Autophagy, 2022, 18:2781-2798.
[8]	Schlein LJ, Thamm DH. NF-κB activation in canine cancer[J]. Vet Pathol, 2022, 59:724-732.

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E3泛素连接酶RNF138抑制溃疡性结肠炎的发生及进展

E3 ubiquitinase RNF138 inhibits the development of ulcerative colitis

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