Affiliation:
1. From INSERM U525, Hopital Saint-Louis (C.M., F.S.), and INSERM U460, Faculté Bichat (O.T.-B.M., M.E.P., P.G.S.), Paris, France. C.M. is presently at The Cleveland Clinic Foundation, Cell Biology Department, 9500 Euclid Ave, Cleveland, OH 44195.
Abstract
Abstract
—Frzb-1 is a secreted protein, presenting similarity with the Wnt-binding domain of the frizzled family of receptors, which acts as an antagonist of Wnt signaling. Using mRNA differential display in the rat aorta balloon injury model, we identified overexpression of
Frzb
-1 mRNA and determined its cDNA sequence. By quantitative reverse transcription–polymerase chain reaction and RNase protection assay, a biphasic upregulation of
rFrzb-1
expression was observed, with significant peaks of a 1.7-fold increase at 4 days and a 1.5-fold increase at 3 weeks after aortic injury in vivo. In contrast, expression of the rat frizzled receptor genes
rfz1
and
rfz2
were transiently downregulated at 1 and 4 hours after balloon injury.
rFrzb-1
was expressed predominantly in rat aortic smooth muscle cells (RASMCs) and barely in aortic fibroblasts and endothelial cells (RAECs), whereas
rfz1
and
rfz2
were expressed in all of these cells when stimulated with serum. Transient downregulation of
rfz1
and
rfz2
expression was reproduced by stimulation of quiescent RASMCs with serum, platelet-derived growth factor-BB, or fibroblast growth factor-2. In contrast,
rFrzb-1
expression diminished slowly, to reach a 2-fold decrease 24 hours after growth factor stimulation, implying that quiescent RASMCs expressed higher levels of
rFrzb-1
mRNA than did proliferative ones. Overexpression of
rFrzb-1
in the aorta seemed to coincide with the arrest of RASMC proliferation occurring in the media 4 days and in the neointima 3 weeks after balloon injury. Our results demonstrate that
rfrzb-1
,
rfz1,
and
rfz2
are differentially regulated in response to arterial injury and that this modulation seems to follow the proliferative state of RASMCs
,
suggesting that these Wnt-signaling components may be involved in intimal vascular disease.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
36 articles.
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