RRC ID 59232
Author Kuroda M, Nishiguchi M, Ugawa N, Ishikawa E, Kawabata Y, Okamoto S, Sasaki W, Miyatake Y, Sebe M, Masumoto S, Tsutsumi R, Harada N, Sakaue H.
Title Interferon regulatory factor 7 mediates obesity-associated MCP-1 transcription.
Journal PLoS One
Abstract Hypertrophy, associated with adipocyte dysfunction, causes increased pro-inflammatory adipokine, and abnormal glucose and lipid metabolism, leading to insulin resistance and obesity-related-health problems. By combining DNA microarray and genomic data analyses to predict DNA binding motifs, we identified the transcription factor Interferon Regulatory Factor 7 (IRF7) as a possible regulator of genes related to adipocyte hypertrophy. To investigate the role of IRF7 in adipocytes, we examined gene expression patterns in 3T3-L1 cells infected with a retrovirus carrying the IRF7 gene and found that enforced IRF7 expression induced the expression of monocyte chemoattractant protein-1 (MCP-1), a key initial adipokine in the chronic inflammation of obesity. CRISPR/Cas9 mediated-suppression of IRF7 significantly reduced MCP-1 mRNA. Luciferase assays, chromatin immunoprecipitation PCR analysis and gel shift assay showed that IRF7 transactivates the MCP-1 gene by binding to its proximal Interferon Stimulation Response Element (ISRE), a putative IRF7 binding motif. IRF7 knockout mice exhibited lower expression of MCP-1 in epidydimal white adipose tissue under high-fat feeding conditions, suggesting the transcription factor is physiologically important for inducing MCP-1. Taken together, our results suggest that IRF7 transactivates MCP-1 mRNA in adipocytes, and it may be involved in the adipose tissue inflammation associated with obesity.
Volume 15(5)
Pages e0233390
Published 2020-1-1
DOI 10.1371/journal.pone.0233390
PII PONE-D-19-33716
PMID 32437400
PMC PMC7241760
MeSH 3T3-L1 Cells Adipocytes / metabolism* Adipose Tissue, White / metabolism Animals Chemokine CCL2 / genetics* Chemokine CCL2 / metabolism Gene Expression Regulation HEK293 Cells Humans Interferon Regulatory Factor-7 / genetics* Interferon Regulatory Factor-7 / metabolism Mice Mice, Knockout Obesity / genetics* Obesity / metabolism Promoter Regions, Genetic
IF 2.74
Times Cited 0
Mice RBRC01420