Regulation of inflammatory phenotype in macrophages by a diabetes-induced long noncoding RNA

MA Reddy, Z Chen, JT Park, M Wang, L Lanting… - Diabetes, 2014 - Am Diabetes Assoc
MA Reddy, Z Chen, JT Park, M Wang, L Lanting, Q Zhang, K Bhatt, A Leung, X Wu, S Putta…
Diabetes, 2014Am Diabetes Assoc
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 …
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.
Am Diabetes Assoc