Regulation of inflammatory phenotype in macrophages by a diabetes-induced long noncoding RNA.
Regulation of inflammatory phenotype in macrophages by a diabetes-induced long noncoding RNA.
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DOI：
10.2337/db14-0298
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发表时间：
2014-12
期刊：
影响因子：
7.7
通讯作者：
Natarajan R
中科院分区：
文献类型：
--
作者：
Reddy MA;Chen Z;Park JT;Wang M;Lanting L;Zhang Q;Bhatt K;Leung A;Wu X;Putta S;Sætrom P;Devaraj S;Natarajan R
巨噬细胞介导与糖尿病并发症相关的炎症增强的机制尚不完全清楚。我们使用RNA测序分析了从糖尿病db/db小鼠中分离的骨髓巨噬细胞的转录组，并鉴定了1,648个与对照db/+小鼠相比差异表达的基因。数据分析显示，糖尿病可能通过参与巨噬细胞功能的转录因子促进了促炎、促纤维化和功能失调的选择性激活巨噬细胞表型。值得注意的是，糖尿病改变了几种长链非编码rna （lncRNAs）的水平。由于lncRNA在糖尿病并发症中的作用尚不清楚，我们进一步表征了lncRNA E330013P06的功能，它在db/db和饮食诱导的胰岛素抵抗型2型糖尿病（T2D）小鼠的巨噬细胞中上调，但在1型糖尿病小鼠中没有上调。在T2D患者的单核细胞中也表达上调。在高糖和棕榈酸处理的小鼠巨噬细胞中，E330013P06也随着炎症基因的增加而增加。巨噬细胞中E330013P06过表达诱导炎症基因，增强对炎症信号的反应，增加泡沫细胞的形成。相反，小干扰rna介导的E330013P06基因沉默抑制了糖尿病刺激诱导的炎症基因。这些结果确定了糖尿病巨噬细胞转录组和巨噬细胞中lncrna的新功能作用，可能导致基于lncrna的炎症性糖尿病并发症治疗。
The mechanisms by which macrophages mediate the enhanced inflammation associated with diabetes complications are not completely understood. We used RNA sequencing to profile the transcriptome of bone marrow macrophages isolated from diabetic db/db mice and identified 1,648 differentially expressed genes compared with control db/+ mice. Data analyses revealed that diabetes promoted a proinflammatory, profibrotic, and dysfunctional alternatively activated macrophage phenotype possibly via transcription factors involved in macrophage function. Notably, diabetes altered levels of several long noncoding RNAs (lncRNAs). Because the role of lncRNAs in diabetes complications is unknown, we further characterized the function of lncRNA E330013P06, which was upregulated in macrophages from db/db and diet-induced insulin-resistant type 2 diabetic (T2D) mice, but not from type 1 diabetic mice. It was also upregulated in monocytes from T2D patients. E330013P06 was also increased along with inflammatory genes in mouse macrophages treated with high glucose and palmitic acid. E330013P06 overexpression in macrophages induced inflammatory genes, enhanced responses to inflammatory signals, and increased foam cell formation. In contrast, small interfering RNA–mediated E330013P06 gene silencing inhibited inflammatory genes induced by the diabetic stimuli. These results define the diabetic macrophage transcriptome and novel functional roles for lncRNAs in macrophages that could lead to lncRNA-based therapies for inflammatory diabetes complications.
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影响因子：
20.1
作者：
Leung A;Trac C;Jin W;Lanting L;Akbany A;Sætrom P;Schones DE;Natarajan R
通讯作者：
Natarajan R
影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
影响因子：
37.8
作者：
Devaraj, S;Jialal, I
通讯作者：
Jialal, I
DOI：
10.1093/bioinformatics/btr209
发表时间：
2011-07-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Lin MF;Jungreis I;Kellis M
通讯作者：
Kellis M
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.