MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice.

MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice.
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DOI:
10.1038/ncomms3883
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发表时间:
2013
影响因子:
16.6
通讯作者:
Ono, Koh
Ono, Koh
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Horie, Takahiro;Nishino, Tomohiro;Baba, Osamu;Kuwabara, Yasuhide;Nakao, Tetsushi;Nishiga, Masataka;Usami, Shunsuke;Izuhara, Masayasu;Sowa, Naoya;Yahagi, Naoya;Shimano, Hitoshi;Matsumura, Shigenobu;Inoue, Kazuo;Marusawa, Hiroyuki;Nakamura, Tomoyuki;Hasegawa, Koji;Kume, Noriaki;Yokode, Masayuki;Kita, Toru;Kimura, Takeshi;Ono, Koh

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MicroRNAs (miRs)是一种小的非蛋白质编码rna,可以结合特定的mRNA并抑制翻译或促进mRNA降解。最近的报道表明,位于固醇调节元件结合蛋白(SREBP) 2内含子内的miR-33可控制胆固醇稳态,可能是治疗动脉粥样硬化的潜在治疗靶点。在这里,我们表明miR-33的缺失导致高脂肪饮食引起的肥胖和肝脏脂肪变性的显著恶化。通过使用miR-33−/−Srebf1+/−小鼠,我们证明SREBP-1是miR-33的靶点,并且在miR-33−/−小鼠中导致肥胖和肝脏脂肪变性的机制涉及SREBP-1的表达增强。这些结果阐明了体内由miR-33介导的SREBP-1和SREBP-2之间的一种新的相互作用。微rna miR-33由编码甾醇调节结合蛋白2 (SREBP-2)基因的内含子编码,并控制胆固醇稳态。在这里,Horie等人发现SREBP-1是miR-33的靶标,并表明miR-33的缺失会促进小鼠饮食诱导的肥胖和肝脏脂肪变性。
MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports have indicated that miR-33, which is located within the intron of sterol regulatory element-binding protein (SREBP) 2, controls cholesterol homoeostasis and may be a potential therapeutic target for the treatment of atherosclerosis. Here we show that deletion of miR-33 results in marked worsening of high-fat diet-induced obesity and liver steatosis. Using miR-33−/−Srebf1+/− mice, we demonstrate that SREBP-1 is a target of miR-33 and that the mechanisms leading to obesity and liver steatosis in miR-33−/− mice involve enhanced expression of SREBP-1. These results elucidate a novel interaction between SREBP-1 and SREBP-2 mediated by miR-33 in vivo. The micro-RNA miR-33 is encoded by an intron of the gene encoding sterol regulatory-binding protein 2 (SREBP-2) and controls cholesterol homoeostasis. Here, Horie et al. identify SREBP-1 as a target of miR-33 and show that deletion of miR-33 promotes diet-induced obesity and liver steatosis in mice.
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