未经证实:微RNA(miRNA)通过抑制基因转录/翻译在转录后水平上充当调控机制,并在细胞应激反应中起核心作用。渗透变化发生在各种疾病中,包括肝硬化和肝性脑病。细胞水合的变化和细胞体积的改变是细胞功能和基因表达的主要调节因子。在这项研究中,研究了响应低渗透压的肝基因表达的调节。
UNASSIGNED:通过基因表达阵列对正常和低渗灌注大鼠肝脏的mRNA分析用于鉴定miRNA及其与细胞增殖前细胞肿胀相关的潜在靶基因。还在用miRNA模拟物处理的分离的肝细胞中研究了选定的miR-141-3p,细胞拉伸,和部分肝切除术后。进行抑制剂灌注研究以解开负责miRNA上调的信号传导途径。
未经评估:使用全基因组转录组学分析,研究表明,低渗暴露导致灌流大鼠肝脏的差异基因表达。此外,miR-141-3p在灌注的大鼠肝脏和原代肝细胞中通过低渗透压上调。与此一致,miR-141-3p上调在Src-,Erk-,和p38-MAPK抑制。此外,荧光素酶报告基因测定表明miR-141-3p靶向细胞周期蛋白依赖性激酶8(Cdk8)mRNA。部分肝切除术在肝细胞增殖开始后短暂上调miR-141-3p水平,而Cdk8mRNA表达下调。大鼠肝细胞的机械拉伸导致miR-141-3p上调,而Cdk8mRNA呈下降趋势。值得注意的是,miR-141-3p过表达抑制Huh7细胞增殖。
UNASSIGNED:在肝细胞中发现了Src介导的miR-141-3p上调,以响应低渗肿胀和机械拉伸。由于其抗增殖功能,miR-141-3p可以反调节由这些刺激触发的增殖效应。
未经批准:在这项研究中,我们将microRNA141-3p鉴定为渗透敏感性miRNA,抑制肝细胞肿胀时的增殖。microRNA141-3p的上调,由Src-控制,Erk-,和p38-MAPK信号,导致参与代谢过程的各种基因的mRNA水平降低,大分子生物合成,和细胞周期进程。
UNASSIGNED: MicroRNAs (miRNAs) act as a regulatory mechanism on a post-transcriptional level by repressing gene transcription/translation and play a central role in the cellular stress response. Osmotic changes occur in a variety of diseases including liver cirrhosis and hepatic encephalopathy. Changes in cell hydration and alterations of the cellular volume are major regulators of cell function and gene expression. In this study, the modulation of hepatic gene expression in response to hypoosmolarity was studied.
UNASSIGNED: mRNA analyses of normo- and hypoosmotic perfused rat livers by gene expression arrays were used to identify miRNA and their potential target genes associated with cell swelling preceding cell proliferation. Selected miR-141-3p was also investigated in isolated hepatocytes treated with miRNA mimic, cell stretching, and after partial hepatectomy. Inhibitor perfusion studies were performed to unravel signalling pathways responsible for miRNA upregulation.
UNASSIGNED: Using genome-wide transcriptomic analysis, it was shown that hypoosmotic exposure led to differential gene expression in perfused rat liver. Moreover, miR-141-3p was upregulated by hypoosmolarity in perfused rat liver and in primary hepatocytes. In concert with this, miR-141-3p upregulation was prevented after Src-, Erk-, and p38-MAPK inhibition. Furthermore, luciferase reporter assays demonstrated that miR-141-3p targets cyclin dependent kinase 8 (Cdk8) mRNA. Partial hepatectomy transiently upregulated miR-141-3p levels just after the initiation of hepatocyte proliferation, whereas Cdk8 mRNA was downregulated. The mechanical stretching of rat hepatocytes resulted in miR-141-3p upregulation, whereas Cdk8 mRNA tended to decrease. Notably, the overexpression of miR-141-3p inhibited the proliferation of Huh7 cells.
UNASSIGNED: Src-mediated upregulation of miR-141-3p was found in hepatocytes in response to hypoosmotic swelling and mechanical stretching. Because of its antiproliferative function, miR-141-3p may counter-regulate the proliferative effects triggered by these stimuli.
UNASSIGNED: In this study, we identified microRNA 141-3p as an osmosensitive miRNA, which inhibits proliferation during liver cell swelling. Upregulation of microRNA 141-3p, controlled by Src-, Erk-, and p38-MAPK signalling, results in decreased mRNA levels of various genes involved in metabolic processes, macromolecular biosynthesis, and cell cycle progression.