title: RAGE-TXNIP axis is required for S100B-promoted Schwann cell migration, fibronectin expression and cytokine secretion.
abstract: During peripheral nerve injury, Schwann cells (SCs) adopt a migratory phenotype and remodel the extracellular matrix and provide a supportive activity for neuron regeneration. SCs synthesize neurotrophic factors and cytokines that are crucial for the repair of the injured nerve. The receptor for advanced glycation end products (RAGE) and its ligand S100B, which are secreted by SCs, are required for the repair of the injured peripheral nerve in vivo. However, the precise intracellular pathways involved have not been completely elucidated. Here, we show that RAGE-induced S100B secretion involves the recruitment of S100B in lipid rafts and caveolae. Moreover, we demonstrate for the first time that RAGE induces the expression of thioredoxin interacting protein (TXNIP) in SCs and the injured sciatic nerve in vivo. TXNIP is involved in the activation of p38 MAPK, CREB and NFκB in SCs. TXNIP silencing partially inhibits RAGE-induced SC migration and completely abolishes RAGE-induced fibronectin and IL-1β expression. Our results support a model in which TXNIP mediates in part RAGE-induced SC migration and is required for the expression of provisional ECM and pro-inflammatory IL-1β. We provide new insight on the role of the SC RAGE-TXNIP axis in the repair of injured peripheral nerves.
authors.affiliation: NICN, CNRS UMR 6184, Faculté de Médecine, Université Aix-Marseille, 13344 Marseille Cedex 15, France.
authors.forename: Oualid
authors.initials: O
authors.lastname: Sbai
authors.forename: Takhellambam S
authors.initials: TS
authors.lastname: Devi
authors.forename: Mariarosa A B
authors.initials: MA
authors.lastname: Melone
authors.forename: Francois
authors.initials: F
authors.lastname: Feron
authors.forename: Michel
authors.initials: M
authors.lastname: Khrestchatisky
authors.forename: Lalit P
authors.initials: LP
authors.lastname: Singh
authors.forename: Lorena
authors.initials: L
authors.lastname: Perrone
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002465:Cell Movement; D004789:Enzyme Activation; D005353:Fibronectins / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism*; D012583:Schwann Cells / Q000166:cytology* / Q000201:enzymology; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D005353:Fibronectins; D053583:Interleukin-1beta; D009414:Nerve Growth Factors; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; C493796:TXNIP protein, rat; D048051:p38 Mitogen-Activated Protein Kinases