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首页> 外文期刊>American Journal of Physiology >Department of Biochemistry and Molecular Biology, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Carson International Cancer Center, Shenzhen University Health Sciences Center, Shenzhen, People's Republic of China
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Department of Biochemistry and Molecular Biology, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Carson International Cancer Center, Shenzhen University Health Sciences Center, Shenzhen, People's Republic of China

机译：广东省豁免疾病的生物化学与分子生物学系，深圳市深圳市人民共和国深圳国际癌症中心科尔森国际癌症中心重点实验室

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There is growing evidence that microRNAs (miRNAs) are implicated in cellular adaptation to osmotic stress, but the underlying osmosignaling pathways are still not completely understood. In this study, we found that a passenger strand miRNA, miR-23a-5p, was significantly downregulated in response to high NaCI treatment in mouse inner medullary collecting duct cells (mlMCD3) through an miRNA profiling assay. The decrease of miR-23a-5p is hypertonicity-dependent and osmotolerant cell type-specific. Knockdown of miR-23a-5p increased cellular survival and proliferation in mlMCD3. In contrast, miR-23a-5p overexpression repressed cell viability and proliferation under hypertonic stress. RNA deep-sequencing revealed that a heat shock protein 70 (HSP70) isoform, HSP70 member 1B (HSPA1B), was significantly increased under hypertonic treatment. Based on the prediction analysis by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and TargetScan, and a further validation via a dual-luciferase assay, HSPA1B was identified as a potential target of miR-23a-5p. Overexpressed miR-23a-5p suppressed HSPA1B, whereas downregulated miR-23a-5p promoted HSPA1B expression in mlMCD3. In addition, an in vivo study demonstrated that there is a reverse correlation between the levels of miR-23a-5p and HSPA1B in mouse renal inner medulla (papilla) that is exposed to extremely high osmolality. In summary, this study elucidates that passenger strand miR-23a-5p is a novel tonicity-responsive miRNA. The downregulation of miR-23a-5p facilitates cellular adaptation to hypertonic stress in mammalian renal cells through modulating HSPA1B.
机译：越来越多的证据表明，microRNA（miRNA）与细胞对渗透胁迫的适应有关，但其潜在的渗透信号通路仍不完全清楚。在这项研究中，我们通过miRNA图谱分析发现，小鼠内髓集合管细胞（mlMCD3）中的乘客链miRNA，miR-23a-5p，因高NaCl处理而显著下调。miR-23a-5p的降低具有高渗依赖性和渗透耐受细胞类型特异性。miR-23a-5p的敲除增加了mlMCD3中的细胞存活和增殖。相反，在高渗应激下，miR-23a-5p的过度表达抑制了细胞的活力和增殖。RNA深度测序显示，在高渗处理下，热休克蛋白70（HSP70）亚型HSP70成员1B（HSPA1B）显著增加。基于基因本体（GO）、京都基因和基因组百科全书（KEGG）和TargetScan的预测分析，以及通过双荧光素酶分析进一步验证，HSPA1B被确定为miR-23a-5p的潜在靶点。过度表达的miR-23a-5p抑制了HSPA1B，而下调的miR-23a-5p促进了mlMCD3中HSPA1B的表达。此外，一项体内研究表明，暴露于极高渗透压的小鼠肾内髓质（乳头）中的miR-23a-5p和HSPA1B水平之间存在反向相关性。总之，本研究阐明了乘客链miR-23a-5p是一种新的张力反应性miRNA。miR-23a-5p的下调通过调节HSPA1B促进哺乳动物肾细胞对高渗应激的细胞适应。

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