Exosomal miR-29b of Gut Origin in Patients With Ulcerative Colitis Suppresses Heart Brain-Derived Neurotrophic Factor.
Exosomal miR-29b of Gut Origin in Patients With Ulcerative Colitis Suppresses Heart Brain-Derived Neurotrophic Factor.
复制标题
溃疡性结肠炎患者肠道来源的外体miR-29b抑制心脏脑源性神经营养因子。
DOI：
10.3389/fmolb.2022.759689
复制
发表时间：
2022
影响因子：
5
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Lian H;Zhong XS;Xiao Y;Sun Z;Shen Y;Zhao K;Ma X;Li Y;Niu Q;Liu M;Powell DW;Liu C;Li Q
背景和目标：虽然以前已经注意到炎症性肠病（IBD）中心脏和肠道之间的相互作用，但发炎的肠道如何损害心脏功能仍然难以理解。我们假设肠道来源的外泌体miRNA诱导IBD的心脏重塑。我们的目的是鉴定不仅具有诊断价值而且有助于溃疡性结肠炎（UC）患者心脏重塑的血浆外泌体miRNA。 方法：从UC患者和健康对照受试者中分离血浆外泌体，并通过下一代测序分析外泌体miRNA。通过RT-qPCR检测CCD 841 CoN结肠上皮细胞中的外泌体miR-29 b水平。将包装有miR-29 b的外来体与H9 c2细胞一起孵育或给予活小鼠。 结果如下：UC患者血浆外泌体miRNA谱与对照组相比有显著差异，包括miR-29 b在内的20种miRNA差异表达。在CCD 841 CoN细胞中，TNFα、IL-1β和H2 O2显著升高了细胞及其分泌的外泌体中的miR-29 b（p < 0.01），表明IBD中肠上皮分泌富含miR-29 b的外泌体。在H9 c2成肌细胞中，miR-29 b调节多个基因，包括脑源性神经营养因子（BDNF）。用miR-29 b包装的上皮细胞来源的外泌体也减弱了BDNF并增加了裂解的半胱天冬酶3，提示细胞凋亡。此外，尾静脉注射具有高水平miR-29 b的工程化外泌体抑制成年小鼠心脏中的BDNF并增加切割的半胱天冬酶3（p < 0.01）。 结论：血浆exosomemiRNA谱可作为IBD诊断的新方法。过量的血浆外泌体miR-29 b抑制IBD中的关键蛋白质如BDNF，导致心脏损害。
Background and Aims: While the interplay between heart and gut in inflammatory bowel disease (IBD) has previously been noted, how the inflamed gut impairs heart function remain elusive. We hypothesized that exosomal miRNAs of gut origin induce cardiac remodeling in IBD. Our aim was to identify plasma exosomal miRNAs that not only are of diagnostic value but also contribute to cardiac remodeling in patients with ulcerative colitis (UC). Methods: Plasma exosomes were isolated from UC patients and healthy control subjects and exosomal miRNAs were profiled by next-generation sequencing. Exosomal miR-29b levels in CCD841 CoN colon epithelial cells were detected by RT-qPCR. Exosomes packaged with miR-29b were incubated with H9c2 cells or administered to live mice. Results: The plasma exosomal miRNA profiles of the UC patients were significantly different from that of the controls and 20 miRNAs including miR-29b were differentially expressed. In CCD841 CoN cells, TNFα, IL-1β, and H2O2 significantly elevated miR-29b in both the cells and their secreted exosomes (p < 0.01), suggesting that intestinal epithelium secrets exosomes rich in miR-29b in IBD. In H9c2 myoblast cells, miR-29b modulated multiple genes including brain-derived neurotrophic factor (BDNF). Epithelial cell-derived exosomes packaged with miR-29b also attenuated BDNF and increased cleaved caspase 3, suggestive of apoptosis. Furthermore, tail vein injection of engineered exosomes with high levels of miR-29b suppressed BDNF and augmented cleaved caspase 3 in the heart of adult mouse (p < 0.01). Conclusion: Plasma exosomal miRNA profile could be a novel diagnostic approach for IBD. Excessive plasma exosomal miR-29b suppresses critical proteins like BDNF in IBD, leading to cardiac impairment.