1: J Biol Chem. 2002 Nov 15;277(46):44485-96. Epub 2002 Aug 27. 

Osteopontin transcription in aortic vascular smooth muscle cells is controlled
by glucose-regulated upstream stimulatory factor and activator protein-1
activities.

Bidder M, Shao JS, Charlton-Kachigian N, Loewy AP, Semenkovich CF, Towler DA.

Division of Bone and Mineral Diseases, Department of Internal Medicine,
Washington University School of Medicine, St. Louis, Missouri 63110, USA.

The expression of the matrix cytokine osteopontin (OPN) is up-regulated in
aortic vascular smooth muscle cells (VSMCs) by diabetes. OPN expression in
cultured VSMCs is reciprocally regulated by glucose and 2-deoxyglucose (2-DG;
inhibitor of cellular glucose metabolism). Systematic analyses of OPN
promoter-luciferase reporter constructs identify a CCTCATGAC motif at
nucleotides -80 to -72 relative to the initiation site that supports OPN
transcription in VSMCs. The region -83 to -45 encompassing this motif confers
basal and glucose- and 2-DG-dependent transcription on an unresponsive promoter.
Competition and gel mobility supershift assays identify upstream stimulatory
factor (USF; USF1:USF2) and activator protein-1 (AP1; c-Fos:c-Jun) in complexes
binding the composite CCTCATGAC element. Glucose up-regulates both AP1 and USF
binding activities 2-fold in A7r5 cells and selectively up-regulates USF1
protein levels. By contrast, USF (but not AP1) binding activity is suppressed by
2-DG and restored by glucose treatment. Expression of either USF or AP1
activates the proximal OPN promoter in A7r5 VSMCs in part via the CCTCATGAC
element. Moreover, glucose stimulates the transactivation functions of c-Fos and
USF1, but not c-Jun, in one-hybrid assays. Mannitol does not regulate binding,
transactivation functions, USF1 protein accumulation, or OPN transcription.
Thus, OPN gene transcription is regulated by USF and AP1 in aortic VSMCs,
entrained to changes in cellular glucose metabolism.

PMID: 12200434 [PubMed - indexed for MEDLINE]


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