論文 - 詳細
| RRC ID | 44628 |
|---|---|
| 著者 | Kitamura H, Kimura S, Shimamoto Y, Okabe J, Ito M, Miyamoto T, Naoe Y, Kikuguchi C, Meek B, Toda C, Okamoto S, Kanehira K, Hase K, Watarai H, Ishizuka M, El-Osta A, Ohara O, Miyoshi I. |
| タイトル | Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation. |
| ジャーナル | FASEB J |
| Abstract |
Macrophages play a critical role in chronic inflammation and metabolic diseases. We identified a longer splice variant of ubiquitin specific protease (USP) 2-69 as a novel molecule that modulates pathways implicated in metabolic disorders. Expression levels of aP2/FABP4 and PAI-1/SERPINE1 genes were increased by 4- and 1.8-fold, respectively, after short hairpin RNA-mediated knockdown (KD) of the USP2 gene, and such expression was alleviated by overexpression of USP2-69 in human myeloid cell lines. Supernatants derived from USP2-KD cells induced IL6 (∼6-fold) and SAA3 (∼15-fold) in 3T3-L1 adipocytes to suggest the anti-inflammatory properties of USP2. In addition, we observed a 30% decrease in the number of macrophages in mesenteric adipose tissue derived from USP2-69 transgenic mice fed a high-fat diet for 14 wk compared with that in their C57BL/6 littermates (P<0.01), which was consistent with a ∼40% decrease in transcription of aP2 and PAI-1. The aP2 locus exhibited elevated chromatin accessibility (>2.1-fold), methylation of histone H3 lysine 4 (>4.5-fold), and acetylation of histone H4 (>2.5-fold) in USP2-KD cells. Transfection of isopeptidase-mutated USP2-69 did not alter chromatin conformation on the aP2 locus in USP2-KD cells. Our results suggest that USP2-69 suppresses meta-inflammatory molecules involved in the development of type-2 diabetes. |
| 巻・号 | 27(12) |
| ページ | 4940-53 |
| 公開日 | 2013-12-1 |
| DOI | 10.1096/fj.13-233528 |
| PII | fj.13-233528 |
| PMID | 24005904 |
| MeSH | Adipocytes / metabolism Animals Cell Line Chromatin / metabolism Chromatin Assembly and Disassembly* Endopeptidases / genetics* Endopeptidases / metabolism Epigenesis, Genetic Histones / metabolism Humans Inflammation / genetics Inflammation / metabolism Interleukin-6 / genetics Interleukin-6 / metabolism Macrophages / metabolism* Mice Mice, Inbred C57BL Myeloid Cells / metabolism Plasminogen Activator Inhibitor 1 / genetics Plasminogen Activator Inhibitor 1 / metabolism Serum Amyloid A Protein / genetics Serum Amyloid A Protein / metabolism Transcription Factor AP-2 / genetics Transcription Factor AP-2 / metabolism Transcription, Genetic* Ubiquitin Thiolesterase Ubiquitin-Specific Proteases / genetics* Ubiquitin-Specific Proteases / metabolism |
| IF | 4.966 |
| 引用数 | 16 |
| WOS 分野 | BIOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| 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 | News |
| 各媒体での言及数の合計 | 6 |
| 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 | |
| ヒト・動物細胞 | HL60(RCB0041) THP-1(RCB1189) |