Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
Adipose tissue microRNAs as regulators of CCL2 production in human obesity.
复制标题
脂肪组织 microRNA 作为人类肥胖中 CCL2 产生的调节因子。
作者：
Arner E;Mejhert N;Kulyté A;Balwierz PJ;Pachkov M;Cormont M;Lorente-Cebrián S;Ehrlund A;Laurencikiene J;Hedén P;Dahlman-Wright K;Tanti JF;Hayashizaki Y;Rydén M;Dahlman I;van Nimwegen E;Daub CO;Arner P
在肥胖症中，白色脂肪组织（WAT）炎症与胰岛素抵抗有关。增加的脂肪细胞趋化因子（C-C基序）配体2（CCL 2）分泌可能通过吸引炎性细胞迁移到组织中而引发脂肪炎症。使用无偏的方法，我们确定了在人类肥胖中失调的脂肪microRNAs（miRNAs），并评估了它们在控制CCL 2产生中的可能作用。在从56名受试者获得的皮下WAT中，11种miRNA存在于所有受试者中，并且在肥胖症中下调。其中，10种影响脂肪细胞CCL 2的体外分泌，2种miRNA（miR-126和miR-193 b）定义了调控回路。虽然miR-126直接与CCL 2 mRNA的3′-非翻译区结合，但miR-193 b通过转录因子网络间接调节CCL 2的产生，其中许多转录因子已在其他炎症条件下被鉴定。此外，miR-193 b和miR-126在人单核细胞/巨噬细胞系中的过表达减弱了CCL 2的产生。皮下WAT中两种miRNA的水平与CCL 2分泌（miR-193 b）和整合素α-X（一种炎症巨噬细胞标记物）（miR-193 b和miR-126）的表达显著相关。总之，我们的数据表明，miRNA可能是脂肪炎症的重要调节因子，通过它们对人类脂肪细胞和巨噬细胞释放CCL 2的影响。
In obesity, white adipose tissue (WAT) inflammation is linked to insulin resistance. Increased adipocyte chemokine (C-C motif) ligand 2 (CCL2) secretion may initiate adipose inflammation by attracting the migration of inflammatory cells into the tissue. Using an unbiased approach, we identified adipose microRNAs (miRNAs) that are dysregulated in human obesity and assessed their possible role in controlling CCL2 production. In subcutaneous WAT obtained from 56 subjects, 11 miRNAs were present in all subjects and downregulated in obesity. Of these, 10 affected adipocyte CCL2 secretion in vitro and for 2 miRNAs (miR-126 and miR-193b), regulatory circuits were defined. While miR-126 bound directly to the 3′-untranslated region of CCL2 mRNA, miR-193b regulated CCL2 production indirectly through a network of transcription factors, many of which have been identified in other inflammatory conditions. In addition, overexpression of miR-193b and miR-126 in a human monocyte/macrophage cell line attenuated CCL2 production. The levels of the two miRNAs in subcutaneous WAT were significantly associated with CCL2 secretion (miR-193b) and expression of integrin, α-X, an inflammatory macrophage marker (miR-193b and miR-126). Taken together, our data suggest that miRNAs may be important regulators of adipose inflammation through their effects on CCL2 release from human adipocytes and macrophages.
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炎症和代谢疾病中的脂肪因子。
DOI：
10.1038/nri2921
发表时间：
2011-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.6
作者：
Fain JN
通讯作者：
Fain JN
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
4.8
作者：
Sell, H;Dietze-Schroeder, D;Eckel, J
通讯作者：
Eckel, J
DOI：
10.1073/pnas.091062498
发表时间：
2001-04-24
影响因子：
11.1
作者：
Tusher, VG;Tibshirani, R;Chu, G
通讯作者：
Chu, G