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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

HucMSC-Ex alleviates inflammatory bowel disease via the lnc78583-mediated miR3202/HOXB13 pathway

Abstract: As a group of nonspecific inflammatory diseases affecting the intestine, inflammatory bowel disease (IBD) exhibits the characteristics of chronic recurring inflammation, and was proven to be increasing in incidence (Kaplan, 2015). IBD induced by genetic background, environmental changes, immune functions, microbial composition, and toxin exposures (Sasson et al., 2021) primarily includes ulcerative colitis (UC) and Crohn's disease (CD) with complicated clinical symptoms featured by abdominal pain, diarrhea, and even blood in stools (Fan et al., 2021; Huang et al., 2021). UC is mainly limited to the rectum and the colon, while CD usually impacts the terminal ileum and colon in a discontinuous manner (Ordás et al., 2012; Panés and Rimola, 2017). In recent years, many studies have suggested the lack of effective measures in the diagnosis and treatment of IBD, prompting an urgent need for new strategies to understand the mechanisms of and offer promising therapies for IBD.

Key words: Inflammatory bowel disease; Mesenchymal stem cell-derived exosome; Long non-coding RNAs; Homeobox B13; miR3202

Chinese Summary  <19> HucMSC-Ex通过调控lnc78583介导的miR3202/HOXB13通路缓解炎症性肠病

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。

关键词组:炎症性肠病;长链非编码RNA(lncRNA);HOXB13;miR3202;间充质干细胞;外泌体


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DOI:

10.1631/jzus.B2100793

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On-line Access:

2022-05-13

Received:

2021-09-15

Revision Accepted:

2022-01-27

Crosschecked:

2022-05-13

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