miR-27 Impairs the Adipogenic Lineage Commitment via Targeting Lysyl Oxidase
miR-27 Impairs the Adipogenic Lineage Commitment via Targeting Lysyl Oxidase
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miR-27 通过靶向赖氨酰氧化酶损害脂肪形成谱系的承诺
DOI：
10.1002/oby.21319
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发表时间：
2015-12-01
期刊：
影响因子：
6.9
通讯作者：
Huang, Hai-Yan
中科院分区：
文献类型：
--
作者：
Chen, Su-Zhen;Xu, Xu;Huang, Hai-Yan
目的：间充质干细胞的募集和投向及其向脂肪细胞的终末分化是肥胖时脂肪细胞数量增加的主要途径。我们以前的研究表明，赖氨酰氧化酶(Lox)在骨形态发生蛋白4(BMP4)诱导的C3H10T1/2细胞脂肪细胞系定向分化过程中上调并发挥重要作用。方法：采用不同BMI的人和高脂饮食的C57BL/6小鼠的脂肪组织样本，比较microRNA-27(miR-27)的表达水平与肥胖的关系。结果：在BMP4处理的C3H10T1/2细胞和人皮下脂肪组织中，Lox表达水平与miR-27表达水平均呈负相关。Lox 3‘非编码区荧光素酶报告实验表明miR-27直接靶向Lox。此外，miR-27的过表达损害了BMP4诱导的Lox的上调和脂肪细胞的承诺，这可以通过过表达成熟的Lox来挽救。相反，通过特定的抑制剂抑制miR-27可以增加Lox的表达和脂肪细胞的承诺。结论：综上所述，这些结果提示miR-27通过靶向Lox来抑制成脂细胞的承诺。
Objective: The recruitment and commitment of mesenchymal stem cells and their terminal differentiation into adipocytes are the main pathways for increasing adipocyte cell numbers during obesity. Our previous studies have shown that lysyl oxidase (Lox) is upregulated and functions as an essential factor during bone morphogenetic protein 4 (BMP4) -induced C3H10T1/2 cell adipocytic lineage commitment. However, the mechanism of Lox regulation during adipogenic lineage commitment has remained largely unestablished.Methods: Samples of adipose tissue from humans with different BMI and C57BL/6 mice with a high-fat diet were used to compare microRNA-27 (miR-27) expression level associated with obesity. Taqman assays were used for miR-27 expression detection and Oil Red O staining for adipogenesis analysis.Results: A negative correlation was identified between Lox expression level and miR-27 expression in both BMP4-treated C3H10T1/2 cells and human subcutaneous adipose tissues. A Lox 3' UTR luciferase reporter assay showed that miR-27 directly targeted Lox. Furthermore, overexpression of miR-27 impaired BMP4-induced upregulation of Lox and adipocytic commitment, which could be rescued by overexpression of mature Lox. Conversely, miR-27 inhibition by specific inhibitors increased Lox expression and adipocytic commitment.Conclusions: Taken together, these results suggest a novel role for miR-27 in repressing adipogenic lineage commitment by targeting Lox.