한빛사 논문
Jinyoung Leea,1, Jung Eun Shinb,1, Bohm Leea, Hyemin Kima, Yewon Jeona, Seung Hyun Ahna, Sung Wook Chia, and Yongcheol Choa,2
aDepartment of Life Sciences, Korea University, 02841 Seoul, Republic of Korea; and bDepartment of Molecular Neuroscience, Dong-A University College of Medicine, 49201 Busan, Republic of Korea
1J.L. and J.E.S. contributed equally to this work.
2To whom correspondence may be addressed.
Abstract
Axon regeneration is regulated by a neuron-intrinsic transcriptional program that is suppressed during development but that can be reactivated following peripheral nerve injury. Here we identify Prom1, which encodes the stem cell marker prominin-1, as a regulator of the axon regeneration program. Prom1 expression is developmentally down-regulated, and the genetic deletion of Prom1 in mice inhibits axon regeneration in dorsal root ganglion (DRG) cultures and in the sciatic nerve, revealing the neuronal role of Prom1 in injury-induced regeneration. Elevating prominin-1 levels in cultured DRG neurons or in mice via adeno-associated virus-mediated gene delivery enhances axon regeneration in vitro and in vivo, allowing outgrowth on an inhibitory substrate. Prom1 overexpression induces the consistent down-regulation of cholesterol metabolism-associated genes and a reduction in cellular cholesterol levels in a Smad pathway-dependent manner, which promotes axonal regrowth. We find that prominin-1 interacts with the type I TGF-β receptor ALK4, and that they synergistically induce phosphorylation of Smad2. These results suggest that Prom1 and cholesterol metabolism pathways are possible therapeutic targets for the promotion of neural recovery after injury.
Prominin-1, sciatic nerve injury, cholesterol metabolism, Smad, Activin
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