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Regulation of Inflammatory Phenotype in Macrophages by a Diabetes-Induced Long Noncoding RNA

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 g...

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Autores principales: Reddy, Marpadga A., Chen, Zhuo, Park, Jung Tak, Wang, Mei, Lanting, Linda, Zhang, Qiang, Bhatt, Kirti, Leung, Amy, Wu, Xiwei, Putta, Sumanth, Sætrom, Pål, Devaraj, Sridevi, Natarajan, Rama
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238007/
https://www.ncbi.nlm.nih.gov/pubmed/25008173
http://dx.doi.org/10.2337/db14-0298
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author Reddy, Marpadga A.
Chen, Zhuo
Park, Jung Tak
Wang, Mei
Lanting, Linda
Zhang, Qiang
Bhatt, Kirti
Leung, Amy
Wu, Xiwei
Putta, Sumanth
Sætrom, Pål
Devaraj, Sridevi
Natarajan, Rama
author_facet Reddy, Marpadga A.
Chen, Zhuo
Park, Jung Tak
Wang, Mei
Lanting, Linda
Zhang, Qiang
Bhatt, Kirti
Leung, Amy
Wu, Xiwei
Putta, Sumanth
Sætrom, Pål
Devaraj, Sridevi
Natarajan, Rama
author_sort Reddy, Marpadga A.
collection PubMed
description 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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spelling pubmed-42380072015-12-01 Regulation of Inflammatory Phenotype in Macrophages by a Diabetes-Induced Long Noncoding RNA Reddy, Marpadga A. Chen, Zhuo Park, Jung Tak Wang, Mei Lanting, Linda Zhang, Qiang Bhatt, Kirti Leung, Amy Wu, Xiwei Putta, Sumanth Sætrom, Pål Devaraj, Sridevi Natarajan, Rama Diabetes Complications 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. American Diabetes Association 2014-12 2014-11-13 /pmc/articles/PMC4238007/ /pubmed/25008173 http://dx.doi.org/10.2337/db14-0298 Text en © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
spellingShingle Complications
Reddy, Marpadga A.
Chen, Zhuo
Park, Jung Tak
Wang, Mei
Lanting, Linda
Zhang, Qiang
Bhatt, Kirti
Leung, Amy
Wu, Xiwei
Putta, Sumanth
Sætrom, Pål
Devaraj, Sridevi
Natarajan, Rama
Regulation of Inflammatory Phenotype in Macrophages by a Diabetes-Induced Long Noncoding RNA
title Regulation of Inflammatory Phenotype in Macrophages by a Diabetes-Induced Long Noncoding RNA
title_full Regulation of Inflammatory Phenotype in Macrophages by a Diabetes-Induced Long Noncoding RNA
title_fullStr Regulation of Inflammatory Phenotype in Macrophages by a Diabetes-Induced Long Noncoding RNA
title_full_unstemmed Regulation of Inflammatory Phenotype in Macrophages by a Diabetes-Induced Long Noncoding RNA
title_short Regulation of Inflammatory Phenotype in Macrophages by a Diabetes-Induced Long Noncoding RNA
title_sort regulation of inflammatory phenotype in macrophages by a diabetes-induced long noncoding rna
topic Complications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238007/
https://www.ncbi.nlm.nih.gov/pubmed/25008173
http://dx.doi.org/10.2337/db14-0298
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