Abstract
The inflammatory response is a critical regulator for the regeneration of axon following nervous system injury. Nuclear factor-kappa B (NF-κB) is characteristically known for its ubiquitous role in the inflammatory response. However, its functional role in adult mammalian axon growth remains elusive. Here, we found that the NF-κB signaling pathway is activated in adult sensory neurons through peripheral axotomy. Furthermore, inhibition of NF-κB in peripheral sensory neurons attenuated their axon growth in vitro and in vivo. Our results also showed that NF-κB modulated axon growth by repressing the phosphorylation of STAT3. Furthermore, activation of STAT3 significantly promoted adult optic nerve regeneration. Taken together, the findings of our study indicated that NF-κB/STAT3 cascade is a critical regulator of intrinsic axon growth capability in the adult nervous system.
Keywords:
NF-κB signaling; STAT3; axon growth; optic nerve.
© 2019 Wiley Periodicals, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies
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Axons / physiology*
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Cells, Cultured
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Female
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Glyceraldehyde 3-Phosphate / pharmacology
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Intracellular Signaling Peptides and Proteins / pharmacology
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Mice
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Mice, Inbred C57BL
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Mice, Inbred ICR
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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Optic Nerve
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Proline / analogs & derivatives
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Proline / pharmacology
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism*
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Regeneration / physiology*
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STAT3 Transcription Factor / antagonists & inhibitors
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism*
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Sciatic Nerve
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Thiocarbamates / pharmacology
Substances
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Antibodies
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Colivelin
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Intracellular Signaling Peptides and Proteins
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Myc protein, mouse
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NF-kappa B
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Proto-Oncogene Proteins c-myc
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STAT3 Transcription Factor
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Stat3 protein, mouse
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Thiocarbamates
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prolinedithiocarbamate
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Glyceraldehyde 3-Phosphate
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Proline