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Antagonism of RAGE suppresses peripheral nerve regeneration
Author(s) -
Rong Ling Ling,
Trojaborg Werner,
Qu Wu,
Kostov Konstantin,
Yan Shi Du,
Gooch Clifton,
Szabolcs Matthias,
Hays Arthur P.,
Schmidt Ann Marie
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-1899com
Subject(s) - sciatic nerve , regeneration (biology) , axotomy , neurite , rage (emotion) , peripheral nerve injury , chemistry , receptor , neuroscience , microbiology and biotechnology , anatomy , medicine , biology , biochemistry , in vitro
Axotomy of peripheral nerve triggers events that coordinate a limited inflammatory response to axonal degeneration and initiation of neurite outgrowth. Inflammatory and neurite outgrowth‐promoting roles for the receptor for advanced glycation end products (RAGE) have been suggested, so we tested its role in peripheral nerve regeneration. Analysis of immunohistochemical localization of RAGE by confocal microscopy revealed that RAGE was expressed in axons and infiltrating mononuclear phagocytes upon unilateral sciatic nerve crush in mice. Administration of soluble RAGE, the extracellular ligand binding domain of RAGE, or blocking F(ab')2 fragments of antibodies raised to either RAGE or its ligands, S100/calgranulins or amphoterin, reduced functional recovery as assessed by motor and sensory nerve conduction velocities and sciatic functional index and reduced regeneration, as assessed by myelinated fiber density after acute crush of the sciatic nerve. In parallel, in mice subjected to RAGE blockade, decreased numbers of mononuclear phagocytes infiltrated the distal nerve segments after crush. These findings provide the first evidence of an innate function of the ligand/RAGE axis and suggest that RAGE plays an important role in regeneration of the peripheral nervous system.—Rong, L. L., Trojaborg, W., Qu, W., Kostov, K., Yan, S. D., Gooch, C., Szabolcs, M., Hays, A. P., Schmidt, A. M. Antagonism of RAGE suppresses peripheral nerve regeneration. FASEB J. 18, 1812–1817 (2004)