MicroRNAs contribute to the maintenance of cell-type-specific physiological characteristics: miR-192 targets Na+/K+-ATPase β1.
MicroRNAs contribute to the maintenance of cell-type-specific physiological characteristics: miR-192 targets Na+/K+-ATPase β1.
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DOI：
10.1093/nar/gks1228
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发表时间：
2013-01
影响因子：
14.9
通讯作者：
Liang M
中科院分区：
文献类型：
--
作者：
Mladinov D;Liu Y;Mattson DL;Liang M
MicroRNAs(MiRNAs)在生物发育和疾病中发挥着重要作用。人们对它们在正常成人生理中的作用知之甚少。肾脏的近曲小管(PCT)和髓质粗升肢(MTAL)由具有不同转运活性的上皮细胞组成。我们鉴定了55对可能的miRNA-靶蛋白，其中许多miRNA及其预测的靶蛋白在PCT和mTAL中反向富含。一些miRNAs似乎对共享靶标具有协同效应。MIR-192及其预测的靶标Na+/K+-ATP酶β-1亚单位(Atp1b1)是一种为肾小管运输提供动力的酶，在肾脏区域呈反向富集。在小鼠中，miR-192的敲除导致Atp1b1蛋白的上调。当小鼠喂食高盐饮食时，miR-192基因的敲除减弱了尿量的适应性增加。有趣的是，miR-192似乎通过5‘-非翻译区而不是3’-非翻译区靶向Atp1b1。这项研究提出了一种新的生理机制，即miR-192抑制Na+/K+-ATPase，并有助于肾脏处理液体平衡。它支持miRNAs在确定可能看起来微妙但在生理上至关重要的细胞特征方面的重要作用。
MicroRNAs (miRNAs) play important roles in biological development and disease. Much less is known about their role in normal adult physiology. The proximal convoluted tubule (PCT) and the medullary thick ascending limb (mTAL) in the kidney consist of epithelial cells with different transport activities. We identified 55 possible miRNA-target pairs of which the miRNAs and their predicted target proteins, many of which are involved in epithelial transport, were inversely enriched in PCT and mTAL. Some miRNAs appeared to have synergistic effects on shared targets. miR-192 and its predicted target the β-1 subunit of Na+/K+-ATPase (Atp1b1), an enzyme providing the driving force for tubular transport, were inversely enriched in kidney regions. In mice, knockdown of miR-192 led to up-regulation of Atp1b1 protein. When mice were fed with a high-salt diet, knockdown of miR-192 blunted the adaptational increase of urine output. Interestingly, miR-192 appeared to target Atp1b1 through the 5′-, rather than 3′-untranslated region. The study suggests a novel physiological mechanism in which miR-192 suppresses Na+/K+-ATPase and contributes to renal handling of fluid balance. It supports an important role of miRNAs in determining cellular characteristics that may appear subtle yet are physiologically critical.
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影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
影响因子：
8.3
作者：
Banday, Anees Ahmad;Lokhandwala, Mustafa F.
通讯作者：
Lokhandwala, Mustafa F.
张力反应性 microRNA 有助于最大限度地诱导渗透调节转录因子 OREBP 以响应高 NaCl 高渗性
影响因子：
14.9
作者：
Huang W;Liu H;Wang T;Zhang T;Kuang J;Luo Y;Chung SS;Yuan L;Yang JY
通讯作者：
Yang JY
影响因子：
13.6
作者：
Elvira-Matelot, Emilie;Zhou, Xiao-ou;Jeunemaitre, Xavier
通讯作者：
Jeunemaitre, Xavier
影响因子：
13.6
作者：
Lin, Dao-Hong;Yue, Peng;Wang, Wen-Hui
通讯作者：
Wang, Wen-Hui