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Nerves and Tissue Repair.
Final rept. 10 Dec 90-9 Jun 94,
INDIANA UNIV FOUNDATION INDIANAPOLIS RESEARCH AND SPONSORED PROGRAMS
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This report covers studies of regenerating peripheral nerves and the effect such nerves exert on regenerative growth of the tissue innervated. The iron-transport protein transferrin is an absolute requirement for cell proliferation and is abundant in peripheral nerves. The hypothesis investigated here is that transferrin is delivered axonally and is involved in the nerve-dependent cell proliferation which characterizes repair in avascular tissues. Amphibian axoloti limb regeneration is a well characterized model system for nerve-dependent reparative growth and was used here in experiments testing the hypothesis. Results include demonstrations that transferrin is present in both axons and Schwann cells of peripheral nerves, that the concentration of this factor increases greatly during regeneration, that transferrin is transported distally in regenerating axons at the expected rate for last axonal transport in amphibians, and is released at the growing tips of such axons. Previous work has shown that when nerves to regenerating axolotl limbs are transected the concentration of transferrin in the distal limb tissue declines rapidly and limb regeneration stops. These results strongly support the hypothesis that neural transferrin is important in nerve-dependent growth during vertebrate limb regeneration. Studies of both transferrin binding and expression of the transferrin gene in cells of axolotl peripheral nerve indicate that both uptake and synthesis of this factor occur in the regenerating nerve. These results have important implications for understanding the trophic effect of nerves in tissue repair.
APPROVED FOR PUBLIC RELEASE