PMID- 24005904
OWN - NLM
STAT- MEDLINE
DCOM- 20140204
LR  - 20201209
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 27
IP  - 12
DP  - 2013 Dec
TI  - Ubiquitin-specific protease 2-69 in macrophages potentially modulates 
      metainflammation.
PG  - 4940-53
LID - 10.1096/fj.13-233528 [doi]
AB  - 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 
      ( approximately 6-fold) and SAA3 ( approximately 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  approximately 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.
FAU - Kitamura, Hiroshi
AU  - Kitamura H
AD  - 1Department of Comparative and Experimental Medicine, Graduate School of Medical 
      Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 
      467-8601, Japan. ktmr@med.nagoya-cu.ac.jp.
FAU - Kimura, Shunsuke
AU  - Kimura S
FAU - Shimamoto, Yoshinori
AU  - Shimamoto Y
FAU - Okabe, Jun
AU  - Okabe J
FAU - Ito, Masatoshi
AU  - Ito M
FAU - Miyamoto, Tomomi
AU  - Miyamoto T
FAU - Naoe, Yoshinori
AU  - Naoe Y
FAU - Kikuguchi, Chisato
AU  - Kikuguchi C
FAU - Meek, Bob
AU  - Meek B
FAU - Toda, Chitoku
AU  - Toda C
FAU - Okamoto, Shiki
AU  - Okamoto S
FAU - Kanehira, Katsushi
AU  - Kanehira K
FAU - Hase, Koji
AU  - Hase K
FAU - Watarai, Hiroshi
AU  - Watarai H
FAU - Ishizuka, Mayumi
AU  - Ishizuka M
FAU - El-Osta, Assam
AU  - El-Osta A
FAU - Ohara, Osamu
AU  - Ohara O
FAU - Miyoshi, Ichiro
AU  - Miyoshi I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130904
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Chromatin)
RN  - 0 (Histones)
RN  - 0 (Interleukin-6)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Serum Amyloid A Protein)
RN  - 0 (Transcription Factor AP-2)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.19.12 (USP2 protein, human)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
RN  - EC 3.4.19.12 (Ubiquitin-Specific Proteases)
RN  - EC 3.4.19.12 (Usp2 protein, mouse)
SB  - IM
MH  - Adipocytes/metabolism
MH  - Animals
MH  - Cell Line
MH  - Chromatin/metabolism
MH  - *Chromatin Assembly and Disassembly
MH  - Endopeptidases/*genetics/metabolism
MH  - Epigenesis, Genetic
MH  - Histones/metabolism
MH  - Humans
MH  - Inflammation/genetics/metabolism
MH  - Interleukin-6/genetics/metabolism
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid Cells/metabolism
MH  - Plasminogen Activator Inhibitor 1/genetics/metabolism
MH  - Serum Amyloid A Protein/genetics/metabolism
MH  - Transcription Factor AP-2/genetics/metabolism
MH  - *Transcription, Genetic
MH  - Ubiquitin Thiolesterase
MH  - Ubiquitin-Specific Proteases/*genetics/metabolism
OTO - NOTNLM
OT  - aP2
OT  - diabetes
OT  - epigenetic control
EDAT- 2013/09/06 06:00
MHDA- 2014/02/05 06:00
CRDT- 2013/09/06 06:00
PHST- 2013/09/06 06:00 [entrez]
PHST- 2013/09/06 06:00 [pubmed]
PHST- 2014/02/05 06:00 [medline]
AID - fj.13-233528 [pii]
AID - 10.1096/fj.13-233528 [doi]
PST - ppublish
SO  - FASEB J. 2013 Dec;27(12):4940-53. doi: 10.1096/fj.13-233528. Epub 2013 Sep 4.