Regulation of CD44 gene expression by the proinflammatory cytokine interleukin-1β in vascular smooth muscle cells

Lauren C. Foster, Burak M. Arkonac, Nicholas E.S. Sibinga, Chengwei Shi, Mark A. Perrella, Edgar Haber

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)20341-20346
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number32
DOIs
StatePublished - Aug 7 1998
Externally publishedYes

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Gene Expression Regulation
Interleukin-1
Vascular Smooth Muscle
Gene expression
Smooth Muscle Myocytes
Muscle
Cells
Cytokines
Arteriosclerosis
Genes
Rats
Neointima
Transplants
Lymphocytes
5' Flanking Region
Transcription
Lymphocyte Activation
Reporter Genes
Cell Movement
Extracellular Matrix

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of CD44 gene expression by the proinflammatory cytokine interleukin-1β in vascular smooth muscle cells. / Foster, Lauren C.; Arkonac, Burak M.; Sibinga, Nicholas E.S.; Shi, Chengwei; Perrella, Mark A.; Haber, Edgar.

In: Journal of Biological Chemistry, Vol. 273, No. 32, 07.08.1998, p. 20341-20346.

Research output: Contribution to journalArticle

Foster, Lauren C. ; Arkonac, Burak M. ; Sibinga, Nicholas E.S. ; Shi, Chengwei ; Perrella, Mark A. ; Haber, Edgar. / Regulation of CD44 gene expression by the proinflammatory cytokine interleukin-1β in vascular smooth muscle cells. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 32. pp. 20341-20346.
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