JNK/ERK/FAK Mediate promigratory actions of basic fibroblast growth factor in astrocytes via CCL2 and COX2

Mathieu P. Lichtenstein, José L.M. Madrigal, Aurora Pujol, Elena Galea

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)

Abstract

While the role of cytokines in causing pro- and anti-inflammatory cascades in the brain and that of chemokines in promoting chemotaxis is well recognized, the immunomodulatory actions of neurotrophins released during brain injury remains largely undetermined. This knowledge gap affects basic fibroblast growth factor (FGF2), which in the brain is mainly produced by astrocytes and characteristically upregulated in reactive astrocytes. The goal of this study was to characterize the inflammatory actions of FGF2 in astrocytes using primary cultures. We report that FGF2 induced the upregulation of monocyte chemoattractant protein (CCL2) and cyclo-oxygenase type 2 (COX2), and the inhibition of lipopolysaccharide-elicited ICAM1 upregulation. The effects of FGF2 were: (i) dependent on gene transcription as revealed by the concomitant regulation of CCL2 or ICAM1 mRNAs; (ii) mediated by the FGF2 receptor type 2; (iii) dependent on ERK, JNK and FAK, and (iv) NF-κB-independent. FGF2 also caused accelerated wound closure dependent on CCL2, COX2, ERK, JNK and FAK in a scratch assay. We conclude that the signaling network triggered by FGF2 in astrocytes converged into accelerating directed motion. It follows that astrocyte migration to injury sites may be a key factor in the repair mechanisms orchestrated by FGF2. Copyright © 2011 S. Karger AG, Basel.
Original languageEnglish
Pages (from-to)86-102
JournalNeuroSignals
Volume20
Issue number2
DOIs
Publication statusPublished - 1 Mar 2012

Keywords

  • Astrocyte
  • Basic fibroblast growth factor
  • c-jun N-terminal kinase
  • Cyclo-oxygenase-2
  • Cytoskeleton
  • Extracellular-signal-regulated kinase
  • Focal adhesion kinase
  • Intercellular adhesion molecule migration
  • Monocyte chemoattractant protein

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