論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC01420 |