| RRC ID |
59232
|
| 著者 |
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.
|
| タイトル |
Interferon regulatory factor 7 mediates obesity-associated MCP-1 transcription.
|
| ジャーナル |
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.
|
| 巻・号 |
15(5)
|
| ページ |
e0233390
|
| 公開日 |
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
|
| 引用数 |
0
|
| リソース情報 |
| 実験動物マウス |
RBRC01420 |
