概要
炎症性肠病(IBD)是一组慢性、复发性肠道炎症, 主要包括溃疡性结肠炎(UC)和克罗恩病(CD)。IBD的发病机制很复杂, 其潜在机制仍不清楚。近年来, 人们对长链非编码RNA(lncRNA)进行了研究, 并将其确定为IBD的潜在生物标志物。在本研究中, 通过使用高通量RNA测序筛选出一种新的lncRNA—lnc78583。前期荧光定量聚合酶链式反应(qRT-PCR)分析结果表明, lnc78583和同源框B13(HOXB13)的mRNA表达水平在IBD患者和炎症状态下的人结直肠黏膜上皮细胞(FHC)中显著降低。为了探索lnc78583在肠道炎症环境中的作用机制, 我们通过对FHC进行lnc78583过表达处理, 发现不仅增加了HOXB13和IL-10的表达, 而且增强了细胞活力, 降低了LDH的释放和p-NF-κB的激活。随后, 我们用人脐带间充质干细胞来源的外泌体(hucMSC-Ex)处理FHC, 结果表明其上调了lnc78583和HOXB13的表达。此外, 进一步预测到miR3202在FHC中和lnc78583以及HOXB13呈负相关作用。lnc78583的过表达下调miR3202, 而miR3202 模拟物显着降低HOXB13的表达水平。综上, 我们的研究初步证明hucMSC-Ex通过lnc78583介导的miR3202/HOXB13通路调节IBD的炎症进程, 从而为IBD提供新的诊断方案和治疗策略。
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Acknowledgments
This work was supported by the Zhenjiang Key Research and Development Plan (Social Development) (No. SH2021066), the Clinical Medical Science and Technology Development Fund Project of Jiangsu University in 2018 (No. JLY20180031), and the Taicang Science and Technology Planning Project (No. TC2020JCYL17), China.
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Yuting XU and Li ZHANG were associated with conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing. Dickson Kofi Wiredu OCANSEY modified the language and edited the article. Bo WANG summarized and drew the diagram of the mechanism. Yilin HOU, Rong MEI, Yongmin YAN, and Xu ZHANG were associated with data analysis and interpretation. Zhaoyang ZHANG and Fei MAO guided the article and provided opinions. All authors have read and approved the final version of the article, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Yuting XU, Li ZHANG, Dickson Kofi Wiredu OCANSEY, Bo WANG, Yilin HOU, Rong MEI, Yongmin YAN, Xu ZHANG, Zhaoyang ZHANG, and Fei MAO declare that they have no conflict of interest.
All participants gave informed consent and this research was performed with the permission of institutions involved and approval from the Ethical Committee of Jiangsu University (No. 2014280).
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Xu, Y., Zhang, L., Ocansey, D.K.W. et al. HucMSC-Ex alleviates inflammatory bowel disease via the lnc78583-mediated miR3202/HOXB13 pathway. J. Zhejiang Univ. Sci. B 23, 423–431 (2022). https://doi.org/10.1631/jzus.B2100793
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DOI: https://doi.org/10.1631/jzus.B2100793