title: Regulation of inflammatory phenotype in macrophages by a diabetes-induced long noncoding RNA.
abstract: 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.
authors.affiliation: Department of Diabetes and Division of Molecular Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA rnatarajan@coh.org mreddy@coh.org.
authors.forename: Marpadga A
authors.initials: MA
authors.lastname: Reddy
authors.affiliation: Department of Diabetes and Division of Molecular Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Diabetes and Division of Molecular Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA.
authors.forename: Jung Tak
authors.initials: JT
authors.lastname: Park
authors.affiliation: Department of Diabetes and Division of Molecular Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Diabetes and Division of Molecular Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA.
authors.forename: Linda
authors.initials: L
authors.lastname: Lanting
authors.affiliation: Department of Diabetes and Division of Molecular Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Diabetes and Division of Molecular Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA.
authors.forename: Kirti
authors.initials: K
authors.lastname: Bhatt
authors.affiliation: Department of Diabetes and Division of Molecular Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA.
authors.forename: Amy
authors.initials: A
authors.lastname: Leung
authors.affiliation: Department of Diabetes and Division of Molecular Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Diabetes and Division of Molecular Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA.
authors.forename: Sumanth
authors.initials: S
authors.lastname: Putta
authors.affiliation: Departments of Computer and Information Science and Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Sætrom
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
authors.affiliation: Department of Diabetes and Division of Molecular Diabetes Research, Beckman Research Institute of City of Hope, Duarte, CA rnatarajan@coh.org mreddy@coh.org.
authors.forename: Rama
authors.initials: R
authors.lastname: Natarajan
mesh_terms: D000328:Adult; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D010641:Phenotype; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000276:immunology; D015854:Up-Regulation
chemical_list: D062085:RNA, Long Noncoding