Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Department of Experimental Pharmacology, Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8854-8862. doi: 10.3892/mmr.2017.7722. Epub 2017 Oct 4.
Human immunodeficiency virus‑1 (HIV‑1) infection severely damages the gut‑associated lymphoid tissue (GALT), the immune system and the gut barrier, which leads to accelerating the disease progression for patients with acquired immune deficiency syndrome (AIDS). Dysregulation of microRNAs (miRNAs) may contribute to this process. However, few studies have investigated the importance of miRNAs in AIDS pathogenesis and progression. The whole miRNA profile of patients with HIV infection from southwest P.R. China and the mode of interaction between HIV‑1 and miRNAs remains to be elucidated. Colon mucosal samples were collected from HIV+ patients and HIV‑ healthy individuals, miRNAs were isolated and subjected to array hybridization in the present study. A total of 476 human and virus‑derived microRNAs were significantly altered in the HIV+ group when compared with the control group (P<0.05), which may be involved in the progression to AIDS. Target genes of the significantly altered miRNAs were predicted using the TargetScan, miRbase and miRanda databases and the 10 shared target genes of upregulated miRNAs and the 391 target genes of downregulated miRNAs were selected. As only 10 target genes were predicted for upregulated miRNAs, subsequent GO and KEGG pathway analyses were focused on the 391 target genes of the downregulated miRNAs. The findings of the present study identified a series of crucial pathways, including cell‑extracellular matrix interaction and chemokine regulation, which indicated close affinity with CD4+ T cell activation. These pathways, involving genes such as integrin α5, led to a gut barrier dysfunction of patients with HIV. Important miRNAs include hsa‑miRNA‑32‑5p, hsa‑miRNA‑195‑5p, hsa‑miRNA‑20b‑5p, hsa‑miRNA‑590‑5p. The expression levels of the miRNAs and their target genes were confirmed using RT‑qPCR. Taking into previous observations, the findings of the present study identified the importance of miRNAs for regulating gut barrier dysfunction via multiple regulatory molecules and signaling pathways, which elucidated the underlying molecular mechanism of gut barrier dysfunction in patients with HIV.
人类免疫缺陷病毒 1（HIV-1）感染严重损害了肠道相关淋巴组织（GALT）、免疫系统和肠道屏障，这导致获得性免疫缺陷综合征（AIDS）患者的疾病进展加速。miRNAs 的失调可能促成了这一过程。然而，很少有研究调查 miRNAs 在艾滋病发病机制和进展中的重要性。来自中国西南地区 HIV 感染者的全 miRNA 谱和 HIV-1 与 miRNAs 之间的相互作用模式仍有待阐明。本研究从 HIV+患者和 HIV-健康个体中采集结肠黏膜样本，分离 miRNA 并进行阵列杂交。与对照组相比，HIV+组共有 476 个人类和病毒来源的 microRNAs 发生显著改变（P<0.05），这可能与艾滋病的进展有关。使用 TargetScan、miRbase 和 miRanda 数据库预测显著改变的 miRNAs 的靶基因，并选择上调 miRNAs 的 10 个共同靶基因和下调 miRNAs 的 391 个靶基因。由于仅预测到上调 miRNAs 的 10 个靶基因，因此随后的 GO 和 KEGG 通路分析集中在下调 miRNAs 的 391 个靶基因上。本研究的发现确定了一系列关键途径，包括细胞-细胞外基质相互作用和趋化因子调节，这与 CD4+T 细胞激活密切相关。这些途径涉及整合素 α5 等基因，导致 HIV 患者的肠道屏障功能障碍。重要的 miRNAs 包括 hsa-miRNA-32-5p、hsa-miRNA-195-5p、hsa-miRNA-20b-5p、hsa-miRNA-590-5p。使用 RT-qPCR 验证了 miRNA 及其靶基因的表达水平。结合之前的观察结果，本研究确定了 miRNAs 通过多个调节分子和信号通路调节肠道屏障功能障碍的重要性，阐明了 HIV 患者肠道屏障功能障碍的潜在分子机制。
