Microvesicle-Shuttled miR-130b Reduces Fat Deposition in Recipient Primary Cultured Porcine Adipocytes by Inhibiting PPAR-γ Expression
Microvesicle-Shuttled miR-130b Reduces Fat Deposition in Recipient Primary Cultured Porcine Adipocytes by Inhibiting PPAR-γ Expression
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DOI：
10.1002/jcp.24486
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发表时间：
2014-05-01
影响因子：
5.6
通讯作者：
Zhao, Ruqian
中科院分区：
文献类型：
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作者：
Pan, Shifeng;Yang, Xiaojing;Zhao, Ruqian
肥胖是一种世界性的流行病，也是心血管疾病和2型糖尿病的危险因素。因此，开发安全有效的抗肥胖药物是一个持续的临床兴趣领域。microrna通过抑制脂肪生成和脂肪生成相关基因的表达，在抗肥胖中发挥重要作用。然而，由于缺乏适当的递送系统，mirna的临床应用一直受到限制。微囊泡（mv）的发现为寻找更有效的药物运输工具提供了新的思路。在之前的研究中，我们证明了miRNA-130b通过抑制PPAR-表达来抑制脂肪沉积。为了证明miRNA-130b是否可以被包装到mv中，并在受体细胞中作为miRNA-130b的内源性形式发挥作用，我们用质粒转染HeLa-229细胞过表达miRNA-130b。这使得HeLa-229细胞能够选择性地将miRNA-130b包装成mv，并主动将富集miRNA-130b的mv分泌到培养基中。我们进一步证实，富含miRNA-130b的mv含有高浓度的Argonaute 2和热休克蛋白90，这两种蛋白已知可保护循环mirna不被降解。将原代培养的猪脂肪细胞暴露于纯化的、富含mirna -130b的mv中，可导致PPAR-表达显著下调，这与脂肪生成和脂肪生成的减少有关。综上所述，我们的研究结果表明，mv可能提供了一种有效的运输系统，用于递送治疗用途的mirna。我们还发现mv穿梭miRNA-130b通过靶向ppar - γ抑制脂肪生成和脂肪生成，并减少受体脂肪细胞中的脂肪沉积。j .细胞。中国生物医学工程学报，2014,31(2):631-639。(c) 2013 Wiley Periodicals, Inc.；
Obesity is a worldwide epidemic, and a risk factor for cardiovascular disease and type 2 diabetes. Consequently, the development of safe and effective anti-obesity drugs is an area of ongoing clinical interest. MicroRNAs play a vital role in anti-obesity by inhibiting the expression of genes involved in adipogenesis and lipogenesis. However, the clinical application of miRNAs has been limited by a lack of appropriate delivery systems. The discovery of microvesicles (MVs) has shed new light on the search for more efficient drug transport tools. In a previous study, we demonstrated that miRNA-130b suppressed fat deposition by inhibiting PPAR- expression. In order to demonstrate whether miRNA-130b can be packaged into MVs and function as an endogenous form of miRNA-130b in recipient cells, we transfected HeLa-229 cells with plasmid to overexpress miRNA-130b. This enabled HeLa-229 cells to selectively package miRNA-130b into MVs and actively secrete the miRNA-130b enriched MVs into the culture media. We further verified that MVs enriched with miRNA-130b contain elevated concentrations of Argonaute 2 and heat shock protein 90 which are known to protect the circulating miRNAs from degradation. Exposure of primary cultured porcine adipocytes to purified, miRNA-130b-enriched MVs resulted in a significant down-regulation of PPAR- expression which was associated with reduced adipogenesis and lipogenesis. Taken together, our results suggest that MVs may provide an effective transport systems for the deliver of miRNAs for therapeutic use. We also showed that MV-shuttled miRNA-130b inhibited adipogenesis and lipogenesis, and reduced fat deposition in recipient adipocytes by targeting PPAR-gamma. J. Cell. Physiol. 229: 631-639, 2014. (c) 2013 Wiley Periodicals, Inc.