UTP Induces Osteopontin Expression through a Coordinate Action of NFκB, Activator Protein-1, and Upstream Stimulatory Factor in Arterial Smooth Muscle Cells
Journal of Biological Chemistry. 2005-01-01; 280(4): 2708-2713
DOI: 10.1074/jbc.m411786200
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1. J Biol Chem. 2005 Jan 28;280(4):2708-13. doi: 10.1074/jbc.M411786200. Epub
2004 Nov 22.
UTP induces osteopontin expression through a coordinate action of NFkappaB,
activator protein-1, and upstream stimulatory factor in arterial smooth muscle
cells.
Renault MA(1), Jalvy S, Potier M, Belloc I, Genot E, Dekker LV, Desgranges C,
Gadeau AP.
Author information:
(1)INSERM, U441 Athérosclérose, Bordeaux 33600, France.
Osteopontin (OPN) is an important chemokinetic agent for several cell types. Our
earlier studies have shown that its expression is essential for uridine
triphosphate (UTP)-mediated migration of vascular smooth muscle cells. We
demonstrated previously that the activation of an AP-1 binding site located 76
bp upstream of the transcription start in the rat OPN promoter is involved in
the induction of OPN expression. In this work, using a luciferase promoter
deletion assay, we identified a new region of the rat OPN promoter (-1837 to
-1757) that is responsive to UTP. This region contains an NFkappaB site located
at -1800 and an Ebox located at -1768. Supershift electrophoretic mobility shift
assay and chromatin immunoprecipitation assays identified NFkappaB and
USF-1/USF-2 as the DNA binding proteins induced by UTP, respectively, for these
two sites. Using dominant negative mutants of IkappaB kinase and USF
transcription factors, we confirmed that NFkappaB and USF-1/USF-2 are involved
in the UTP-mediated expression of OPN. Using a pharmacological approach, we
demonstrated that USF proteins are regulated by the extracellular
signal-regulated kinase (ERK)1/2 pathway, just as the earlier discovered AP-1
complex, whereas NFkappaB is up-regulated through PKCdelta signals. Finally, our
work suggests that the UTP-stimulated OPN expression involves a coordinate
regulation of PKCdelta-NFkappaB, ERK1/2-USF, and ERK1/2/NAD(P)H oxidase AP-1
signaling pathways.
DOI: 10.1074/jbc.M411786200
PMID: 15557322 [Indexed for MEDLINE]