TY - JOUR
T1 - Regulation of CD44 gene expression by the proinflammatory cytokine interleukin-1β in vascular smooth muscle cells
AU - Foster, Lauren C.
AU - Arkonac, Burak M.
AU - Sibinga, Nicholas E.S.
AU - Shi, Chengwei
AU - Perrella, Mark A.
AU - Haber, Edgar
PY - 1998/8/7
Y1 - 1998/8/7
N2 - 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)-1β. Treatment of rat aortic SMC with IL-1β resulted in a 5.3-fold increase in cell surface CD44 expression. Northern analysis showed that IL-1β 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-1β 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-1β. Regulation of CD44 gene expression by the proinflammatory cytokine IL-1β may contribute to SMC phenotypic modulation in the pathogenesis of arteriosclerosis.
AB - 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)-1β. Treatment of rat aortic SMC with IL-1β resulted in a 5.3-fold increase in cell surface CD44 expression. Northern analysis showed that IL-1β 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-1β 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-1β. Regulation of CD44 gene expression by the proinflammatory cytokine IL-1β may contribute to SMC phenotypic modulation in the pathogenesis of arteriosclerosis.
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U2 - 10.1074/jbc.273.32.20341
DO - 10.1074/jbc.273.32.20341
M3 - Article
C2 - 9685385
AN - SCOPUS:0032493649
SN - 0021-9258
VL - 273
SP - 20341
EP - 20346
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 32
ER -