Fibrinogen inhibits neurite outgrowth via β3 integrin-mediated phosphorylation of the EGF receptor

Christian Schachtrup, Paul Lu, Leonard L. Jones, Jae Lee, Jerry Lu, Ben D. Sachs, Binhai Zheng, Katerina Akassoglou

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Changes in the molecular and cellular composition of the CNS after injury or disease result in the formation of an inhibitory environment that inhibits the regeneration of adult mammalian CNS neurons. Although a dramatic change in the CNS environment after traumatic injury or disease is hemorrhage because of vascular rupture or leakage of the blood-brain barrier, the potential role for blood proteins in repair processes remains unknown. Here we show that the blood protein fibrinogen is an inhibitor of neurite outgrowth that is massively deposited in the spinal cord after injury. We show that fibrinogen acts as a ligand for β3 integrin and induces the transactivation of EGF receptor (EGFR) in neurons. Fibrinogen-mediated inhibition of neurite outgrowth is reversed by blocking either β3 integrin or phoshorylation of EGFR. Inhibition of Src family kinases that mediate the cross-talk between integrin and growth factor receptors rescue the fibrinogen-induced phosphorylation of EGFR. These results identify fibrinogen as the first blood-derived inhibitor of neurite outgrowth and suggest fibrinogen-induced EGFR transactivation on neuronal cells as a molecular link between vascular and neuronal damage in the CNS after injury.

Original languageEnglish
Pages (from-to)11814-11819
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number28
DOIs
StatePublished - Jul 10 2007
Externally publishedYes

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Keywords

  • Blood-brain barrier
  • Regeneration
  • Scar
  • Spinal cord injury
  • Transactivation

ASJC Scopus subject areas

  • Genetics
  • General

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