RAGE modulates peripheral nerve regeneration via recruitment of both inflammatory and axonal outgrowth pathways

Ling Rong Ling, Shi Fang Yan, Thoralf Wendt, Diana Hans, Sophia Pachydaki, Loredana G. Bucciarelli, Adebukola Adebayo, Wu Qu, Yan Lu, Konstantin Rostov, Evanthia Lalla, Du Yan Shi, Clifton Gooch, Matthias Szabolcs, Werner Trojaborg, Arthur P. Hays, Ann Marie Schmidt

Research output: Contribution to journalArticlepeer-review

Abstract

Axotomy of peripheral nerve stimulates events in multiple cell types that initiate a limited inflammatory response to axonal degeneration and simultaneous outgrowth of neurites into the distal segments after injury. We found that pharmacological blockade of RAGE impaired peripheral nerve regeneration in mice subjected to RAGE blockade and acute crush of the sciatic nerve. As our studies revealed that RAGE was expressed in axons and in infiltrating mononuclear phagocytes upon injury, we tested the role of RAGE in these distinct cell types on nerve regeneration. Transgenic mice expressing signal transduction-deficient RAGE in mononuclear phagocytes or peripheral neurons were generated and subjected to unilateral crush injury to the sciatic nerve. Transgenic mice displayed decreased functional and morphological recovery compared with littermate controls, as assessed by motor and sensory conduction velocities; and myelinated fiber density. In double transgenic mice expressing signal transduction deficient RAGE in both mononuclear phagocytes and peripheral neurons, regeneration was even further impaired, suggesting the critical interplay between RAGE-modulated inflammation and neurite outgrowth in nerve repair. These findings suggest that RAGE signaling in inflammatory cells and peripheral neurons plays an important role in plasticity of the peripheral nervous system.

Original languageEnglish
Pages (from-to)1818-1825
Number of pages8
JournalFASEB Journal
Volume18
Issue number15
DOIs
Publication statusPublished - Dec 2004

Keywords

  • Sciatic nerve
  • Signal transduction
  • Transgenic mice

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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