CREB Mediates UTP-Directed Arterial Smooth Muscle Cell Migration and Expression of the Chemotactic Protein Osteopontin via Its Interaction with Activator Protein-1 Sites
| Autor: | Claude Desgranges, Sandra Jalvy, Annabel Reynaud, Laetitia Lam Shang Leen, Alain-Pierre Gadeau, Isabelle Belloc, Marie-Ange Renault |
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| Rok vydání: | 2007 |
| Předmět: |
Smooth muscle cell migration
MAP Kinase Signaling System Physiology p38 mitogen-activated protein kinases Myocytes Smooth Muscle Uridine Triphosphate Biology Response Elements CREB Muscle Smooth Vascular stomatognathic system Cell Movement Gene expression RNA Messenger Phosphorylation Cyclic AMP Response Element-Binding Protein Promoter Regions Genetic Protein kinase A Transcription factor Cells Cultured Activator (genetics) Cyclic AMP-Dependent Protein Kinases Molecular biology Transcription Factor AP-1 biology.protein Osteopontin Cardiology and Cardiovascular Medicine Chromatin immunoprecipitation |
| Zdroj: | Circulation Research. 100:1292-1299 |
| ISSN: | 1524-4571 0009-7330 |
| Popis: | The transcription factor cAMP responsive element-binding protein (CREB) has been found to be involved in arterial smooth muscle cell (SMC) migration. We previously demonstrated that osteopontin (OPN) expression is a key step for UTP-mediated migration of arterial SMCs and that activator protein (AP)-1, nuclear factor κB, and upstream stimulatory transcription factors are involved in this OPN expression. The present study aims to determine the role of CREB in UTP-induced migration and OPN expression in cultured SMCs. We found that CREB is activated by UTP via extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase pathways but not by protein kinase A. Both overexpression of a dominant negative CREB and CREB small interfering RNA treatment suppressed UTP-induced OPN expression and SMC migration. Gel-shift and chromatin immunoprecipitation assays revealed that CREB binds 2 AP-1 sites (−1870 and −76) and a cAMP responsive element–like site (−1403) on the OPN promoter. Mutations of these sites showed that only the 2 AP-1 sites were required for UTP-induced OPN expression. Moreover, gel-supershift and sequential chromatin immunoprecipitation assays suggested that CREB was associated with c-Fos on the AP-1 sites of the OPN promoter. These results demonstrate that CREB participates in the induction of UTP-activated OPN expression via its binding to 2 AP-1 sites and is thus involved in UTP-mediated SMC migration. |
| Databáze: | OpenAIRE |
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