B-Myb regulates the A2B adenosine receptor in vascular smooth muscle cells

✍ Scribed by Cynthia St. Hilaire; Dan Yang; Barbara M. Schreiber; Katya Ravid

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 336 KB
• Volume: 103
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21586

✦ Synopsis

Abstract

The A~2B~ adenosine receptor (A~2B~AR) has been described to control various vascular functions, including inhibition of smooth muscle cell proliferation. Here, we sought to understand the regulation of A~2B~AR gene expression in aortic vascular smooth muscle cells (VSMCs), with a focus on the proliferation phase. Assays with A~2B~AR‐β‐gal aortic VSMCs, in which the endogenous A~2B~AR gene promoter drives the expression of prokaryotic β‐galactosidase (β‐gal) instead of the endogenous A~2B~AR gene, show that β‐gal expression is upregulated when the cells are induced to exit from cell cycle arrest. Similarly, the level of A~2B~AR mRNA is upregulated in proliferating primary aortic VSMCs. In search of related mechanisms, it was noted that the A~2B~AR gene promoter contains several putative binding sites for the proliferation‐inducing transcription factor, B‐Myb. Using a clone of the 5′ region upstream of the mouse A~2B~AR gene linked to a reporter gene, B‐Myb site deletion mutants were generated. It was determined that B‐Myb upregulates the A~2B~AR gene promoter, and specific promoter binding sites were identified as functional. In accordance, B‐Myb also elevates endogenous A~2B~AR mRNA and receptor activity, and this activity decreases cell proliferation. Our data are novel in that they show that this proliferation‐inhibiting A~2B~AR is itself an inducible receptor regulated by B‐Myb. J. Cell. Biochem. 103: 1962–1974, 2007. © 2007 Wiley‐Liss, Inc.