Determining the influence of high glucose on exosomal lncRNAs, mRNAs, circRNAs and miRNAs derived from human renal tubular epithelial cells.
Determining the influence of high glucose on exosomal lncRNAs, mRNAs, circRNAs and miRNAs derived from human renal tubular epithelial cells.
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确定高葡萄糖对人肾小管上皮细胞来源的外泌体 lncRNA、mRNA、circRNA 和 miRNA 的影响
DOI：
10.18632/aging.202656
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发表时间：
2021-03-10
期刊：
影响因子：
--
通讯作者：
Liu Z
中科院分区：
文献类型：
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作者：
Zhou S;Fang J;Hu M;Pan S;Liu D;Xing G;Liu Z
糖尿病肾病是一种致命的疾病，可导致慢性肾病和终末期肾病。外泌体是一种纳米级的细胞外囊泡，密切参与细胞间的通讯。最重要的是，外泌体在疾病的发生和发展中起着关键作用。然而，外泌体在糖尿病肾病进展中的功能尚未完全阐明。在本研究中，我们确定了在高糖（HG）处理或不处理的人肾小管上皮细胞外泌体中lncRNAs、mrna、circRNAs和miRNAs的表达谱和差异。HG挑战HK-2细胞分泌的外泌体（HG组）与对照组（NC组）相比，共有169个lncrna、885个mrna、3个circrna和152个mirna差异表达。通过基因本体（GO）和京都基因与基因组百科全书（KEGG）分析，研究了差异表达mrna、与差异表达lncRNAs共定位或共表达的mrna （DElncRNAs）、miRNAs潜在靶基因和circRNAs源基因的功能。根据这些差异表达的rna，我们建立了一个集成的circRNA-lncRNA-miRNA-mRNA调控网络。总之，我们的研究表明，外泌体lncRNAs、mrna、circRNAs和miRNAs参与了糖尿病肾病的进展，可能是糖尿病肾病的生物标志物和治疗靶点。
Diabetic nephropathy is a lethal disease that can lead to chronic kidney disease and end-stage kidney disease. Exosomes, which are nanosized extracellular vesicles, are closely involved in intercellular communication. Most importantly, exosomes play critical roles in disease occurrence and development. However, the function of exosomes in diabetic nephropathy progression has not been fully elucidated. In the present study, we determined the expression profiles and differences of lncRNAs, mRNAs, circRNAs and miRNAs in exosomes derived from human renal tubular epithelial cells with or without high glucose (HG) treatment. A total of 169 lncRNAs, 885 mRNAs, 3 circRNAs and 152 miRNAs were differentially expressed in exosomes secreted by HG-challenged HK-2 cells (HG group) compared with controls (NC group). The functions of differentially expressed mRNAs, mRNAs colocalized or coexpressed with differentially expressed lncRNAs (DElncRNAs), potential target genes of miRNAs and source genes of circRNAs were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. According to these differentially expressed RNAs, we established an integrated circRNA-lncRNA-miRNA-mRNA regulatory network. In conclusion, our study suggested that exosomal lncRNAs, mRNAs, circRNAs and miRNAs participate in the progression of diabetic nephropathy and may be possible biomarkers and therapeutic targets in diabetic nephropathy.