Galectin-1 Regulates Initial Axonal Growth in Peripheral Nerves after Axotomy

Abstract

The signals that prompt the axons to send out processes in peripheral nerves after axotomy are not well understood. Here, we report that galectin-1 can play an important role in this initial stage. We developed an in vitro nerve regeneration model that allows us to monitor the initial axon and support cell outgrowth from the proximal nerve stump, which is comparable to the initial stages of nerve repair. We isolated a factor secreted from COS1 cells that enhanced axonal regeneration, and we identified the factor as galectin-1. Recombinant human galectin-1 (rhGAL-1) showed the same activity at low concentrations (50 pg/ml) that are two orders of magnitude lower than those of lectin activity. A similarly low concentration was also effective in in vivo experiments of axonal regeneration with migrating reactive Schwann cells to a grafted silicone tube after transection of adult rat peripheral nerve. Moreover, the application of functional anti-rhGAL-1 antibody strongly inhibited the regeneration in vivo as well as in vitro. The same effect of rhGAL-1 was confirmed in crush/freeze experiments of the adult mouse sciatic nerve. Because galectin-1 is expressed in the regenerating sciatic nerves as well as in both sensory neurons and motor neurons, we suggest that galectin-1 may regulate initial repair after axotomy. This high activity of the factor applied under nonreducing conditions suggests that galectin-1 may work as a cytokine, not as a lectin.

A carbohydrate-binding protein, Galectin-1, promotes proliferation of adult neural stem cells

“…To investigate the in vivo function of Galectin-1, we examined its expression in the mouse brain by using a Galectin-1-specific Ab (29). To confirm the specificity and sensitivity of the staining procedures, brain sections from a galectin-1-null mutant mouse (30) were simultaneously incubated with the same anti-Galectin-1 Ab, and we observed no staining (Fig.…”

“…4 H-J; P Ͻ 0.01; n Ͼ 3 each). Furthermore, infusion of an anti-Galectin-1 neutralizing Ab (29) into the LV of adult wildtype mice significantly decreased the number of slowly dividing cells (Fig. 12, which is published as supporting information on the PNAS web site), a phenotype similar to that seen in galectin-1-null mutants (Fig.…”

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

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ΔFosB, but not FosB, induces delayed apoptosis independent of cell proliferation in the Rat1a embryo cell line

“…5,13 Anti-rhGal-1 was used to detect galectin-1, 46 Figure 7 Suppression of delayed cell death by caspase inhibitors. Quiescent Rat1a(ER-DFosB) cells were cultured with 1 mM estrogen for 36 h, and were then maintained in the absence (hatched bar) or presence (closed bar) of 20 mM zLEHD-fmk (a), 40 mM zDEVD-fmk (b) and 20 mM zIETD-fmk (c).…”