期刊
NEURON
卷 88, 期 4, 页码 720-734出版社
CELL PRESS
DOI: 10.1016/j.neuron.2015.09.050
关键词
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资金
- National Institutes of Health [DE022000, NS082446]
- Hope Center for Neurological Disorders Just In-Time Award
- Hope Center Viral Vectors Core at Washington University School of Medicine
- University of Missouri Spinal Cord Injuries Research Program
- National Research Foundation of Korea [NRF-2012R1A6A3A03039290]
- Wings for Life [WFL-US-002/13]
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 1 alpha (HIF-1 alpha) controls multiple injury-induced genes in sensory neurons and contribute to the preconditioning lesion effect. Knockdown of HIF-1 alpha in vitro or conditional knock out in vivo impairs sensory axon regeneration. The HIF-1 alpha target gene Vascular Endothelial Growth Factor A (VEGFA) is expressed in injured neurons and contributes to stimulate axon regeneration. Induction of HIF-1 alpha 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-1 alpha represents a critical transcriptional regulator in regenerating neurons and suggests hypoxia as a tool to stimulate axon regeneration.
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