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

38 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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