The stem cell marker Prom1 promotes axon regeneration by down-regulating cholesterol synthesis via Smad signaling
DC Field | Value | Language |
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dc.contributor.author | Lee, Jinyoung | - |
dc.contributor.author | Shin, Jung Eun | - |
dc.contributor.author | Lee, Bohm | - |
dc.contributor.author | Kim, Hyemin | - |
dc.contributor.author | Jeon, Yewon | - |
dc.contributor.author | Ahn, Seung Hyun | - |
dc.contributor.author | Chi, Sung Wook | - |
dc.contributor.author | Cho, Yongcheol | - |
dc.date.accessioned | 2021-08-30T19:38:53Z | - |
dc.date.available | 2021-08-30T19:38:53Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2020-07-07 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/54421 | - |
dc.description.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 adenoassociated 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-beta 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. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.subject | PLASMA-MEMBRANE PROTRUSIONS | - |
dc.subject | HEMATOPOIETIC STEM | - |
dc.subject | INTRINSIC CONTROL | - |
dc.subject | EPITHELIAL-CELLS | - |
dc.subject | GROWTH-FACTOR | - |
dc.subject | PROMININ | - |
dc.subject | PROTEIN | - |
dc.subject | CNS | - |
dc.subject | BINDING | - |
dc.subject | CD133 | - |
dc.title | The stem cell marker Prom1 promotes axon regeneration by down-regulating cholesterol synthesis via Smad signaling | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Chi, Sung Wook | - |
dc.contributor.affiliatedAuthor | Cho, Yongcheol | - |
dc.identifier.doi | 10.1073/pnas.1920829117 | - |
dc.identifier.scopusid | 2-s2.0-85088207239 | - |
dc.identifier.wosid | 000548341000024 | - |
dc.identifier.bibliographicCitation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.117, no.27, pp.15955 - 15966 | - |
dc.relation.isPartOf | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.citation.title | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.citation.volume | 117 | - |
dc.citation.number | 27 | - |
dc.citation.startPage | 15955 | - |
dc.citation.endPage | 15966 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | PLASMA-MEMBRANE PROTRUSIONS | - |
dc.subject.keywordPlus | HEMATOPOIETIC STEM | - |
dc.subject.keywordPlus | INTRINSIC CONTROL | - |
dc.subject.keywordPlus | EPITHELIAL-CELLS | - |
dc.subject.keywordPlus | GROWTH-FACTOR | - |
dc.subject.keywordPlus | PROMININ | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | CNS | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | CD133 | - |
dc.subject.keywordAuthor | Prominin-1 | - |
dc.subject.keywordAuthor | sciatic nerve injury | - |
dc.subject.keywordAuthor | cholesterol metabolism | - |
dc.subject.keywordAuthor | Smad | - |
dc.subject.keywordAuthor | Activin | - |
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