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

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.

journal_name

Neuron

journal_title

Neuron

authors

Cho Y,Shin JE,Ewan EE,Oh YM,Pita-Thomas W,Cavalli V

doi

10.1016/j.neuron.2015.09.050

subject

Has Abstract

pub_date

2015-11-18 00:00:00

pages

720-34

issue

4

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(15)00839-9

journal_volume

88

pub_type

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