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J Biol Chem, Vol. 273, Issue 32, 20341-20346, August 7, 1998
From the Cardiovascular Biology Laboratory, The CD44 gene codes for a family of alternatively
spliced, multifunctional adhesion molecules that participate in
extracellular matrix binding, lymphocyte activation, cell migration,
and tumor metastasis. In a mouse model of transplant-associated
arteriosclerosis, CD44 protein was induced in the neointima of
allografted vessels and colocalized with a subset of proliferating
vascular smooth muscle cells (SMC). To elucidate the molecular
mechanisms regulating CD44 expression in this model, we investigated
the regulation of CD44 gene expression by interleukin (IL)-1
Regulation of CD44 Gene Expression by the Proinflammatory
Cytokine Interleukin-1
in Vascular Smooth Muscle Cells
§,¶, and
Department of Medicine,
.
Treatment of rat aortic SMC with IL-1 resulted in a 5.3-fold
increase in cell surface CD44 expression. Northern analysis showed
that IL-1 promoted a dose- and time-dependent
induction of CD44 mRNA which reached 6.6-fold after 48 h, and
nuclear run-on analysis showed that IL-1 increased the rate of CD44
gene transcription within 8 h of stimulation. In transient
reporter gene transfection experiments in rat aortic SMC, a
1.4-kilobase fragment of the mouse CD44 5'-flanking sequence mediated
this response to IL-1. Regulation of CD44 gene expression by the
proinflammatory cytokine IL-1 may contribute to SMC phenotypic modulation in the pathogenesis of arteriosclerosis.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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