Affiliation:
1. Department
of Neuroscience (D13), Osaka University Graduate School of Medicine,
Yamadaoka 2-2, Suita, Osaka
565-0871
2. Department of Fixed
Prosthodontics, Osaka University Graduate School of Dentistry,
1-8 Yamadaoka, Suita, Osaka 565-0871, Japan
Abstract
ABSTRACT
During
the onset and progression of atherosclerosis, the vascular smooth
muscle cell (VSMC) phenotype changes from differentiated to
dedifferentiated, and in some cases, this change is accompanied by
osteogenic transition, resulting in vascular calcification. One
characteristic of dedifferentiated VSMCs is the down-regulation of
smooth muscle cell (SMC) marker gene expression. Bone morphogenetic
proteins (BMPs), which are involved in the induction of osteogenic gene
expression, are detected in calcified vasculature. In this study, we
found that the BMP2-, BMP4-, and BMP6-induced expression of Msx
transcription factors (Msx1 and Msx2) preceded the down-regulation of
SMC marker expression in cultured differentiated VSMCs. Either Msx1 or
Msx2 markedly reduced the myocardin-dependent promoter activities of
SMC marker genes (SM22α and caldesmon). We further investigated
interactions between Msx1 and myocardin/serum response factor
(SRF)/CArG-box motif (
cis
element for SRF) using
coimmunoprecipitation, gel-shift, and chromatin immunoprecipitation
assays. Our results showed that Msx1 or Msx2 formed a ternary complex
with SRF and myocardin and inhibited the binding of SRF or
SRF/myocardin to the CArG-box motif, resulting in inhibition of their
transcription.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
75 articles.
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