Hepatocytes derived extracellular vesicles from high-fat diet induced obese mice modulate genes expression and proliferation of islet β cells
Hepatocytes derived extracellular vesicles from high-fat diet induced obese mice modulate genes expression and proliferation of islet β cells
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高脂饮食诱导肥胖小鼠的肝细胞来源的细胞外囊泡调节胰岛β细胞的基因表达和增殖
DOI：
10.1016/j.bbrc.2019.06.124
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发表时间：
2019-09-03
影响因子：
3.1
通讯作者：
Yang, Tao
中科院分区：
文献类型：
--
作者：
Fu, Qi;Li, Yue;Yang, Tao
肝脏分泌增殖因子，参与肥胖和胰岛素抵抗期间胰岛的代偿性增生。细胞外囊泡（EV）通过向受体细胞传递内部因子来介导细胞间通讯。这项研究探讨了肥胖期间肝细胞 EV 对胰岛 β 细胞的生物学影响。与标准饮食（CD）相比，来自高脂饮食（FWD）诱导的肥胖小鼠的肝细胞EV促进了细胞系MIN6细胞的增殖，但不影响其胰岛素分泌。微阵列分析发现，HFD 和 CD 组的肝细胞 EV 中有 13 个 miRNA 的表达存在显着差异。同时，RNA测序检测到分别用HFD和CD肝细胞EV处理的MIN6细胞中存在显着差异表达的80个基因。通过综合 TargetScan 预测和 RNA 测序结果，预筛选了 6 个 miRNA 和 11 个潜在靶基因。经过miRNA模拟转染并测试靶基因表达和细胞活力后，证实miR-7218-5p通过靶向CD74基因影响MIN6细胞增殖。 siRNA转染和双荧光素酶报告基因测定进一步证实了miRNA-7218-5p对CD74的结合和调节。这些发现表明，HFD 诱导的肥胖可能会改变肝细胞 EV 中的 miRNA 谱，从而调节多个基因的表达和 MIN6 细胞的增殖，并可能介导胰岛的代偿性增生。 (C) 2019 Elsevier Inc. 保留所有权利。
Liver secretes proliferative factors participating compensatory hyperplasia of islets during obesity and insulin resistance. Extracellular vesicles (EVs) mediate intercellular communication by delivering inner factors to recipient cells. This study explored the biological effects of hepatocellular EVs on islet beta cells during obesity. Compared with standard chow diet (CD), hepatocellular EVs derived from high-fat diet (FWD) induced obese mice promoted proliferation of cell line-MIN6 cells, but didn't influence their insulin secretion. Microarray analysis found 13 miRNAs with significantly differential expression in hepatocellular EVs between HFD with CD group. Meanwhile, RNA-sequencing detected 80 genes with significantly differential expression in MIN6 cells treated with HFD and CD hepatocellular EVs respectively. Six miRNAs and 11 potential target genes were pre-screened by synthesizing TargetScan prediction and RNA-sequencing results. After miRNA mimic transfection and testing the expressions of target genes and cell vitality, miR-7218-5p was verified to affect MIN6 cell proliferation through targeting CD74 gene. SiRNA transfection and dual luciferase reporter assay further confirmed the binding and regulation of miRNA-7218-5p on CD74. These findings suggest HFD induced obesity could change miRNA profiles in hepatocellular EVs, which modulate expression of multiple genes and proliferation of MIN6 cells and maybe mediate compensatory hyperplasia of islets. (C) 2019 Elsevier Inc. All rights reserved.