PMID- 23769804
OWN - NLM
STAT- MEDLINE
DCOM- 20140415
LR  - 20211021
IS  - 1096-0023 (Electronic)
IS  - 1043-4666 (Print)
IS  - 1043-4666 (Linking)
VI  - 64
IP  - 1
DP  - 2013 Oct
TI  - AUF1-RGG peptides up-regulate the VEGF antagonist, soluble VEGF receptor-1 
      (sFlt-1).
PG  - 337-42
LID - S1043-4666(13)00263-9 [pii]
LID - 10.1016/j.cyto.2013.05.019 [doi]
AB  - The macrophage is essential to the innate immune response, but also contributes 
      to human disease by aggravating inflammation. Under severe inflammation, 
      macrophages and other immune cells over-produce immune mediators, including 
      vascular endothelial growth factor (VEGF). The VEGF protein stimulates macrophage 
      activation and induces macrophage migration. A natural inhibitor of VEGF, the 
      soluble VEGF receptor (sFlt-1) is also produced by macrophages and sFlt-1 has 
      been used clinically to block VEGF. In macrophages, we have shown that the mRNA 
      regulatory protein AUF1/hnRNP D represses VEGF gene expression by inhibiting 
      translation of AURE-regulated VEGF mRNA. Peptides (AUF1-RGG peptides) that are 
      modeled on the arginine-glycine-glycine (RGG) motif in AUF1 also block VEGF 
      expression. This report shows that the AUF1-RGG peptides reduce two other 
      AURE-regulated genes, TNF and GLUT1. Three alternative splice variants of sFlt-1 
      contain AURE in their 3'UTR, and in an apparent paradox, AUF1-RGG peptides 
      stimulate expression of these three sFlt-1 Variants. The AUF1-RGG peptides likely 
      act by distinct mechanisms with complimentary effects to repress VEGF gene 
      expression and over-express the endogenous VEGF blocking agent, sFlt-1. The 
      AUF1-RGG peptides are novel reagents that reduce VEGF and other inflammatory 
      mediators, and may be useful tools to suppress severe inflammation.
CI  - Published by Elsevier Ltd.
FAU - Fellows, Abigail
AU  - Fellows A
AD  - Veterans Administration Research Service, White River Junction, VT 05009, USA; 
      Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH 
      03755, USA.
FAU - Mierke, Dale F
AU  - Mierke DF
FAU - Nichols, Ralph C
AU  - Nichols RC
LA  - eng
GR  - P20 RR016437/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130614
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (HNRNPD protein, human)
RN  - 0 (Heterogeneous Nuclear Ribonucleoprotein D0)
RN  - 0 (Heterogeneous-Nuclear Ribonucleoprotein D)
RN  - 0 (Hnrpd protein, mouse)
RN  - 0 (Peptides)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Slc2a1 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, mouse)
RN  - EC 2.7.10.1 (Flt1 protein, mouse)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
SB  - IM
MH  - 3' Untranslated Regions/genetics
MH  - Animals
MH  - Cell Line
MH  - Glucose Transporter Type 1/biosynthesis
MH  - Heterogeneous Nuclear Ribonucleoprotein D0
MH  - Heterogeneous-Nuclear Ribonucleoprotein D/*pharmacology
MH  - Humans
MH  - Inflammation/*immunology
MH  - Macrophages/immunology/*metabolism
MH  - Mice
MH  - Peptides/pharmacology
MH  - Protein Isoforms/biosynthesis/genetics
MH  - Protein Structure, Tertiary
MH  - RNA, Messenger/biosynthesis
MH  - Tumor Necrosis Factor-alpha/biosynthesis
MH  - U937 Cells
MH  - Vascular Endothelial Growth Factor A/*antagonists & inhibitors
MH  - Vascular Endothelial Growth Factor Receptor-1/*biosynthesis/genetics
PMC - PMC3770750
MID - NIHMS485560
OTO - NOTNLM
OT  - AU-rich element
OT  - AUF1
OT  - AUF1-RGG
OT  - AURE
OT  - GLUT1
OT  - RGG
OT  - Soluble VEGFR-1
OT  - TNF
OT  - UTR
OT  - VEGF
OT  - arginine-glycine-glycine
OT  - arginine-glycine-glycine region of AUF1
OT  - glucose transporter-1
OT  - hnRNP D
OT  - sFlt-1
OT  - soluble VEGF receptor-1 (sVEGFR-1)
OT  - the AUF1/hnRNP-D mRNA binding protein
OT  - tumor necrosis factor-alpha
OT  - untranslated region of mRNA
OT  - vascular endothelial growth factor
EDAT- 2013/06/19 06:00
MHDA- 2014/04/16 06:00
PMCR- 2014/10/01
CRDT- 2013/06/18 06:00
PHST- 2013/02/20 00:00 [received]
PHST- 2013/04/16 00:00 [revised]
PHST- 2013/05/17 00:00 [accepted]
PHST- 2013/06/18 06:00 [entrez]
PHST- 2013/06/19 06:00 [pubmed]
PHST- 2014/04/16 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - S1043-4666(13)00263-9 [pii]
AID - 10.1016/j.cyto.2013.05.019 [doi]
PST - ppublish
SO  - Cytokine. 2013 Oct;64(1):337-42. doi: 10.1016/j.cyto.2013.05.019. Epub 2013 Jun 
      14.