Enhanced proliferation of cultured human vascular smooth muscle cells linked to increased function of RNA-binding protein HuR

Rudolf Pullmann, Magdalena Juhaszova, Isabel López De Silanes, Tomoko Kawai, Krystyna Mazan-Mamczarz, Marc K. Halushka, Myriam Gorospe

Research output: Contribution to journalArticle

Abstract

In dividing cells, the RNA-binding protein HuR associates with and stabilizes labile mRNAs encoding proliferative proteins, events that are linked to the increased cytoplasmic presence of HuR. Here, assessment of HuR levels in various vascular pathologies (intimal hyperplasia, atherosclerosis and neointimal proliferation, sclerosis of arterialized saphenous venous graft, and fibromuscular dysplasia) revealed a distinct increase in HuR expression and cytoplasmic abundance within the intima and neointima layers. On the basis of these observations, we postulated a role for HuR in promoting the proliferation of vascular smooth muscle cells. To test this hypothesis directly, we investigated the expression, subcellular localization, and proliferative influence of HuR in human vascular smooth muscle cells (hVSMCs). Treatment of hVSMCs with platelet-derived growth factor increased HuR levels in the cytoplasm, thereby influencing the expression of metabolic, proliferative, and structural genes. Importantly, knockdown of HuR expression by using RNA interference caused a reduction of hVSMC proliferation, both basally and following platelet-derived growth factor treatment. We propose that HuR contributes to regulating hVSMC growth and homeostasis in pathologies associated with vascular smooth muscle proliferation.

Original languageEnglish (US)
Pages (from-to)22819-22826
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number24
DOIs
StatePublished - Jun 17 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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