2013年12月
Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation
FASEB Journal
- 巻
- 27
- 号
- 12
- 開始ページ
- 4940
- 終了ページ
- 4953
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1096/fj.13-233528
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.-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. Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation. © FASEB.
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.-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. Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation. © FASEB.
- リンク情報
- ID情報
-
- DOI : 10.1096/fj.13-233528
- ISSN : 1530-6860
- eISSN : 1530-6860
- PubMed ID : 24005904
- SCOPUS ID : 84890504097