Defects of the endoplasmic reticulum and changes to lipid droplet size in mammary epithelial cells due to miR-30b-5p overexpression are correlated to a reduction in Atlastin 2 expression
Defects of the endoplasmic reticulum and changes to lipid droplet size in mammary epithelial cells due to miR-30b-5p overexpression are correlated to a reduction in Atlastin 2 expression
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DOI：
10.1016/j.bbrc.2019.03.022
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发表时间：
2019-04-30
影响因子：
3.1
通讯作者：
Le Provost, Fabienne
中科院分区：
文献类型：
--
作者：
Le Guillou, Sandrine;Laubier, Johann;Le Provost, Fabienne
在哺乳期间，乳腺上皮细胞以乳脂球的形式分泌脂肪，这些乳脂球来自细胞内的脂滴。这些液滴可能从内质网重新形成，也可能来自现有的脂滴；然后它们生长，要么是因为三酰甘油合成的酶从网状结构转移到它们的表面，要么是由于与其他液滴的融合和裂变。MiR-30b-5p在发育中的小鼠乳腺中过表达会损害哺乳，其中包括脂滴大小的增加。本研究旨在了解转基因小鼠中观察到的影响脂滴的这种缺陷的来源。电子显微镜分析显示，转基因小鼠乳腺上皮细胞中的内质网管状网络支离破碎且不连续。与野生型小鼠相比，转基因小鼠的牛奶脂肪酸组成发生了改变，中链饱和脂肪酸水平降低，长链单不饱和脂肪酸比例增加。此外，对microRNA靶标的研究发现，由于miR-30b-5p的过表达，ATLASTIN 2(一种被描述为在脂滴形成中发挥关键作用的GTPase)的显著下调。我们的结果表明，在转基因小鼠的乳房上皮细胞中观察到的脂滴尺寸的增加可能是由于对ATL2表达的直接修饰导致脂滴的形成和分泌的改变，以及miR-30b-5p的过表达导致内质网形态的间接改变。(C)2019年提交人。由爱思唯尔公司出版。
During lactation, mammary epithelial cells secrete fat in the form of milk fat globules that originate from intracellular lipid droplets. These droplets may form de novo from the endoplasmic reticulum or be derived from existing lipid droplets; they then either grow because enzymes of triacylglycerol synthesis relocate from the reticulum to their surface, or due to fusion and fission with other droplets. The overexpression of miR-30b-5p in the developing mouse mammary gland impairs lactation, which includes an increase in lipid droplet size. This study was performed to understand the origin of this defect affecting lipid droplets observed in transgenic mice.Electron microscopy analyses revealed a fragmented and discontinued tubular network of endoplasmic reticulum in the mammary epithelial cells of transgenic mice. The milk fatty acid composition was modified, with lower levels of medium-chain saturated fatty acids and a proportional increase in long-chain monounsaturated fatty acids in transgenic versus wild-type mice. Further, investigations of microRNA targets revealed a significant downregulation of ATLASTIN 2 (a GTPase described as playing a key role in lipid droplet formation) due to miR-30b-5p overexpression.Our results suggest that the increase in lipid droplet size observed in the mammary epithelial cells of transgenic mice might result from changes to lipid droplet formation and secretion because of direct modifications to Atl2 expression and indirect changes to endoplasmic reticulum morphology resulting from the overexpression of miR-30b-5p. (C) 2019 The Authors. Published by Elsevier Inc.