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

Yongcheol Cho, Jung Eun Shin, Eric Edward Ewan, Young Mi Oh, Wolfgang Pita-Thomas, Valeria Cavalli

Research output: Contribution to journalArticle

51 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)720-734
Number of pages15
JournalNeuron
Volume88
Issue number4
DOIs
Publication statusPublished - 2015 Nov 18

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Hypoxia-Inducible Factor 1
Axons
Regeneration
Wounds and Injuries
Genes
Sensory Receptor Cells
Neurons
Neuromuscular Junction
Multiple Trauma
Motor Neurons
Vascular Endothelial Growth Factor A
Hypoxia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Activating Injury-Responsive Genes with Hypoxia Enhances Axon Regeneration through Neuronal HIF-1α. / Cho, Yongcheol; Shin, Jung Eun; Ewan, Eric Edward; Oh, Young Mi; Pita-Thomas, Wolfgang; Cavalli, Valeria.

In: Neuron, Vol. 88, No. 4, 18.11.2015, p. 720-734.

Research output: Contribution to journalArticle

Cho, Yongcheol ; Shin, Jung Eun ; Ewan, Eric Edward ; Oh, Young Mi ; Pita-Thomas, Wolfgang ; Cavalli, Valeria. / Activating Injury-Responsive Genes with Hypoxia Enhances Axon Regeneration through Neuronal HIF-1α. In: Neuron. 2015 ; Vol. 88, No. 4. pp. 720-734.
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