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Regulation of inflammatory gene expression by diabetes induced long noncoding RNA in macrophages (711.1)
Author(s) -
Reddy Marpadga,
Chen Zhuo,
Park JungTak,
Wang Mei,
Lanting Linda,
Zhang Qian,
Wu Xiewie,
Putta Sumanth,
Natarajan Rama
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.711.1
Subject(s) - gene silencing , inflammation , long non coding rna , macrophage , biology , gene expression , macrophage polarization , fibrosis , microbiology and biotechnology , gene , cancer research , immunology , rna , phenotype , medicine , genetics , in vitro
Long noncoding RNAs (lncRNAs) regulate gene expression in diverse patho‐physiological conditions, but their role in diabetes complications is not clear. We hypothesized that diabetes induced lncRNAs could mediate macrophage dysfunction implicated in vascular complications. We profiled gene expression in bone marrow derived macrophages (BMM) from type 2 diabetic db/db and control db/+ mice, after differentiation with GMCSF or MCSF. RT‐QPCR showed dysregulated polarization of BMM from db/db mice. RNA‐Seq revealed differential expression of 2000 transcripts including lncRNAs in BMM from db/db mice relative to db/+ mice. Differentially expressed genes were enriched in networks relevant to fibrosis, adhesion and inflammation, suggesting altered regulation of macrophage function. We validated the increased expression of a lncRNA E330013P06 (E33) in BMM and peritoneal macrophages from db/db and diet induced type 2 diabetic mice as well as macrophages treated with high glucose and palmitic acid. Furthermore, overexpression and siRNA mediated gene silencing demonstrated that E33 can increase inflammatory genes and foam cell formation in macrophages, establishing a novel role for a diabetes induced lncRNA in key macrophage functions involved in diabetic complications. Our findings suggest that understanding of lncRNA dependent mechanisms in macrophages could lead to novel therapeutic interventions. Grant Funding Source : NIH‐NIDDK