Identification of oxidized galectin-1 as an initial repair regulatory factor after axotomy in peripheral nerves

Various neurotrophic factors that promote axonal regeneration have been inv estigated in vivo, but the signals that prompt the axons to send our proces ses in peripheral nerves after axotomy are not well understood. We have sho wn using two specific strategies that galectin-1 can play an important role in this initial stage. One used an in vitro nerve regeneration model that allowed us to monitor the initial axon and support cell outgrowth from the proximal nerve stump comparable to the initial stages of nerve repair. The other strategy was to clarify the axonal regeneration-promoting factor from kidney-derived cells. Using these strategies, we discovered that oxidized galectin-1 from the cell (COS1 cell)conditioned media acts as an axonal reg eneration-promoting factor without the lectin activity. Oxidized recombinan t human galectin-1 (rhGAL-1/Ox) showed the same activity at low concentrati ons (pg/ml range). A similarly low concentration also effectively promoted axonal regeneration in both transection and crush experiments in vivo. More over the application of functional anti-galectin-1 antibody strongly inhibi ted the regeneration in vivo. Since galectin-1 was shown to be secreted and localized in the regenerating sciatic nerve, this suggests that secreted g alectin-1 may be oxidized and change its molecular structure to regulate in itial repair after axotomy as a kind of cytokine. (C) 2000 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.