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Article: Caveolin-1 plays a crucial role in inhibiting neuronal differentiation of neural stem/progenitor cells via VEGF signaling-dependent pathway

TitleCaveolin-1 plays a crucial role in inhibiting neuronal differentiation of neural stem/progenitor cells via VEGF signaling-dependent pathway
Authors
Issue Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2011, v. 6 n. 8, article no. e22901 How to Cite?
AbstractIn the present study, we aim to elucidate the roles of caveolin-1(Cav-1), a 22 kDa protein in plasma membrane invaginations, in modulating neuronal differentiation of neural progenitor cells (NPCs). In the hippocampal dentate gyrus, we found that Cav-1 knockout mice revealed remarkably higher levels of vascular endothelial growth factor (VEGF) and the more abundant formation of newborn neurons than wild type mice. We then studied the potential mechanisms of Cav-1 in modulating VEGF signaling and neuronal differentiation in isolated cultured NPCs under normoxic and hypoxic conditions. Hypoxic embryonic rat NPCs were exposed to 1% O 2 for 24 h and then switched to 21% O 2 for 1, 3, 7 and 14 days whereas normoxic NPCs were continuously cultured with 21% O 2. Compared with normoxic NPCs, hypoxic NPCs had down-regulated expression of Cav-1 and up-regulated VEGF expression and p44/42MAPK phosphorylation, and enhanced neuronal differentiation. We further studied the roles of Cav-1 in inhibiting neuronal differentiation by using Cav-1 scaffolding domain peptide and Cav-1-specific small interfering RNA. In both normoxic and hypoxic NPCs, Cav-1 peptide markedly down-regulated the expressions of VEGF and flk1, decreased the phosphorylations of p44/42MAPK, Akt and Stat3, and inhibited neuronal differentiation, whereas the knockdown of Cav-1 promoted the expression of VEGF, phosphorylations of p44/42MAPK, Akt and Stat3, and stimulated neuronal differentiation. Moreover, the enhanced phosphorylations of p44/42MAPK, Akt and Stat3, and neuronal differentiation were abolished by co-treatment of VEGF inhibitor V1. These results provide strong evidence to prove that Cav-1 can inhibit neuronal differentiation via down-regulations of VEGF, p44/42MAPK, Akt and Stat3 signaling pathways, and that VEGF signaling is a crucial target of Cav-1. The hypoxia-induced down-regulation of Cav-1 contributes to enhanced neuronal differentiation in NPCs. © 2011 Li et al.
Persistent Identifierhttp://hdl.handle.net/10722/138131
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong RGC777610M
774808M
University of Hong Kong200807176043
Dr. Wong BL family donation
Funding Information:

This work was supported by Hong Kong RGC General Research Fund (GRF No. 777610M, No. 774808M, JS), Small Project Funding of the University of Hong Kong (200807176043, JS) and Dr. Wong BL family donation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorLi, Yen_HK
dc.contributor.authorLuo, Jen_HK
dc.contributor.authorLau, WMen_HK
dc.contributor.authorZheng, Gen_HK
dc.contributor.authorFu, Sen_HK
dc.contributor.authorWang, TTen_HK
dc.contributor.authorZeng, HPen_HK
dc.contributor.authorSo, KFen_HK
dc.contributor.authorChung, SKen_HK
dc.contributor.authorTong, Yen_HK
dc.contributor.authorLiu, Ken_HK
dc.contributor.authorShen, Jen_HK
dc.date.accessioned2011-08-26T14:41:16Z-
dc.date.available2011-08-26T14:41:16Z-
dc.date.issued2011en_HK
dc.identifier.citationPLoS One, 2011, v. 6 n. 8, article no. e22901en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/138131-
dc.description.abstractIn the present study, we aim to elucidate the roles of caveolin-1(Cav-1), a 22 kDa protein in plasma membrane invaginations, in modulating neuronal differentiation of neural progenitor cells (NPCs). In the hippocampal dentate gyrus, we found that Cav-1 knockout mice revealed remarkably higher levels of vascular endothelial growth factor (VEGF) and the more abundant formation of newborn neurons than wild type mice. We then studied the potential mechanisms of Cav-1 in modulating VEGF signaling and neuronal differentiation in isolated cultured NPCs under normoxic and hypoxic conditions. Hypoxic embryonic rat NPCs were exposed to 1% O 2 for 24 h and then switched to 21% O 2 for 1, 3, 7 and 14 days whereas normoxic NPCs were continuously cultured with 21% O 2. Compared with normoxic NPCs, hypoxic NPCs had down-regulated expression of Cav-1 and up-regulated VEGF expression and p44/42MAPK phosphorylation, and enhanced neuronal differentiation. We further studied the roles of Cav-1 in inhibiting neuronal differentiation by using Cav-1 scaffolding domain peptide and Cav-1-specific small interfering RNA. In both normoxic and hypoxic NPCs, Cav-1 peptide markedly down-regulated the expressions of VEGF and flk1, decreased the phosphorylations of p44/42MAPK, Akt and Stat3, and inhibited neuronal differentiation, whereas the knockdown of Cav-1 promoted the expression of VEGF, phosphorylations of p44/42MAPK, Akt and Stat3, and stimulated neuronal differentiation. Moreover, the enhanced phosphorylations of p44/42MAPK, Akt and Stat3, and neuronal differentiation were abolished by co-treatment of VEGF inhibitor V1. These results provide strong evidence to prove that Cav-1 can inhibit neuronal differentiation via down-regulations of VEGF, p44/42MAPK, Akt and Stat3 signaling pathways, and that VEGF signaling is a crucial target of Cav-1. The hypoxia-induced down-regulation of Cav-1 contributes to enhanced neuronal differentiation in NPCs. © 2011 Li et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCaveolin 1 - genetics - metabolism-
dc.subject.meshCell Differentiation - genetics - physiology-
dc.subject.meshNeural Stem Cells - cytology - metabolism-
dc.subject.meshSignal Transduction - genetics - physiology-
dc.subject.meshVascular Endothelial Growth Factor A - genetics - metabolism-
dc.titleCaveolin-1 plays a crucial role in inhibiting neuronal differentiation of neural stem/progenitor cells via VEGF signaling-dependent pathwayen_HK
dc.typeArticleen_HK
dc.identifier.emailSo, KF: hrmaskf@hku.hken_HK
dc.identifier.emailChung, SK: skchung@hkucc.hku.hken_HK
dc.identifier.emailTong, Y: tongyao@hku.hken_HK
dc.identifier.emailShen, J: shenjg@hku.hken_HK
dc.identifier.authoritySo, KF=rp00329en_HK
dc.identifier.authorityChung, SK=rp00381en_HK
dc.identifier.authorityTong, Y=rp00509en_HK
dc.identifier.authorityShen, J=rp00487en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0022901en_HK
dc.identifier.pmid21826216-
dc.identifier.pmcidPMC3149620-
dc.identifier.scopuseid_2-s2.0-79961090750en_HK
dc.identifier.hkuros190873en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79961090750&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue8en_HK
dc.identifier.spage22901en_US
dc.identifier.spagearticle no. e22901-
dc.identifier.epage22901en_US
dc.identifier.epagearticle no. e22901-
dc.identifier.eissn1932-6203-
dc.identifier.isiWOS:000293558900042-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, Y=26643036800en_HK
dc.identifier.scopusauthoridLuo, J=8780499000en_HK
dc.identifier.scopusauthoridLau, WM=16239172000en_HK
dc.identifier.scopusauthoridZheng, G=23969618100en_HK
dc.identifier.scopusauthoridFu, S=49061099400en_HK
dc.identifier.scopusauthoridWang, TT=8834035200en_HK
dc.identifier.scopusauthoridZeng, HP=7401472015en_HK
dc.identifier.scopusauthoridSo, KF=34668391300en_HK
dc.identifier.scopusauthoridChung, SK=7404292976en_HK
dc.identifier.scopusauthoridTong, Y=9045384000en_HK
dc.identifier.scopusauthoridLiu, K=7404200456en_HK
dc.identifier.scopusauthoridShen, J=7404929947en_HK

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