AUF1-RGG peptides up-regulate the VEGF antagonist, soluble VEGF receptor-1 (sFlt-1).
Cytokine
; 64(1): 337-42, 2013 Oct.
Article
en En
| MEDLINE
| ID: mdl-23769804
ABSTRACT
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.
Palabras clave
AU-rich element; AUF1; AUF1-RGG; AURE; GLUT1; RGG; Soluble VEGFR-1; TNF; UTR; VEGF; arginine-glycine-glycine; arginine-glycine-glycine region of AUF1; glucose transporter-1; hnRNP D; sFlt-1; soluble VEGF receptor-1 (sVEGFR-1); the AUF1/hnRNP-D mRNA binding protein; tumor necrosis factor-α; untranslated region of mRNA; vascular endothelial growth factor
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptor 1 de Factores de Crecimiento Endotelial Vascular
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Ribonucleoproteína Heterogénea-Nuclear Grupo D
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Factor A de Crecimiento Endotelial Vascular
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Inflamación
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Macrófagos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cytokine
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos