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Neuron. 2015 Nov 18;88(4):720-34. doi: 10.1016/j.neuron.2015.09.050. Epub 2015 Oct 29.

Activating Injury-Responsive Genes with Hypoxia Enhances Axon Regeneration through Neuronal HIF-1α.

Author information

1
Department of Anatomy and Neurobiology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
2
Department of Developmental Biology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
3
Department of Anatomy and Neurobiology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA. Electronic address: cavalli@pcg.wustl.edu.

Abstract

Injured peripheral neurons successfully activate a proregenerative transcriptional program to enable axon regeneration and functional recovery. How transcriptional regulators coordinate the expression of such program remains unclear. Here we show that hypoxia-inducible factor 1α (HIF-1α) controls multiple injury-induced genes in sensory neurons and contribute to the preconditioning lesion effect. Knockdown of HIF-1α in vitro or conditional knock out in vivo impairs sensory axon regeneration. The HIF-1α target gene Vascular Endothelial Growth Factor A (VEGFA) is expressed in injured neurons and contributes to stimulate axon regeneration. Induction of HIF-1α using hypoxia enhances axon regeneration in vitro and in vivo in sensory neurons. Hypoxia also stimulates motor neuron regeneration and accelerates neuromuscular junction re-innervation. This study demonstrates that HIF-1α represents a critical transcriptional regulator in regenerating neurons and suggests hypoxia as a tool to stimulate axon regeneration.

PMID:
26526390
PMCID:
PMC4655162
DOI:
10.1016/j.neuron.2015.09.050
[Indexed for MEDLINE]
Free PMC Article

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