Caveolin-1 plays a crucial role in inhibiting neuronal differentiation of neural stem/progenitor cells via VEGF signaling-dependent pathway
In 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...
Gespeichert in:
| Veröffentlicht in: | PloS one 2011-08, Vol.6 (8), p.e22901-e22901 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e22901 |
|---|---|
| container_issue | 8 |
| container_start_page | e22901 |
| container_title | PloS one |
| container_volume | 6 |
| creator | Li, Yue Luo, Jianmin Lau, Wui-Man Zheng, Guoqing Fu, Shuping Wang, Ting-Ting Zeng, He-Ping So, Kwok-Fai Chung, Sookja Kim Tong, Yao Liu, Kejian Shen, Jiangang |
| description | In 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% O₂ for 24 h and then switched to 21% O₂ for 1, 3, 7 and 14 days whereas normoxic NPCs were continuously cultured with 21% O₂. 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. |
| doi_str_mv | 10.1371/journal.pone.0022901 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1306897822</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A476883345</galeid><doaj_id>oai_doaj_org_article_1a0c9fc3019040b3bb40a1e627eeaa00</doaj_id><sourcerecordid>A476883345</sourcerecordid><originalsourceid>FETCH-LOGICAL-c691t-36b3ccde0ed1f85c7ea76dfa6d20f5df51b8ed67e13722cc7adb96de204cfc23</originalsourceid><addsrcrecordid>eNqNk99q2zAUxs3YWLtubzA2wWBjF0n1x5btm0IpbRcoFLbSWyFLR46KI3mSnS3PsJee3KSlGb0YMkjo_M53rE86Wfae4DlhJTm-82Nwspv33sEcY0prTF5kh6RmdMYpZi-frA-yNzHeYVywivPX2QElFeWU8MPsz5lcg--smxHUd3ITkUQqjMrKDgXfAbIufUvb2MG6FjkYg09VkbbGQAA3WDlY75A397EUiQOsjvvgW3B28AEp6LqI1lai2_PLCxRtm_KT1kxDD04nCdTLYflLbt5mr4zsIrzbzUfZzcX5zdm32dX15eLs9GqmeE2GGeMNU0oDBk1MVagSZMm1kVxTbAptCtJUoHkJySZKlSqlbmqugeJcGUXZUfZxK9t3PoqdjVEQhnlVlxWdiMWW0F7eiT7YlQwb4aUV9xs-tEKGwaoOBJFY1UYxTGqc44Y1TY4lAU5LACkxTlonu2pjswKt0nmTS3ui-xFnl6L1a8FIXk93d5R92QkE_3OEOIiVjZOp0oEfo6gqiquyKKpEfvqHfP5wO6qV6f-tMz6VVZOmOM1LXlWM5UWi5s9QaWhYWZWenLFpfy_h615CYgb4PbRyjFEsfnz_f_b6dp_9_IRdguyGZfTdOL26uA_mW1AFH2MA8-gxwWLqmAc3xNQxYtcxKe3D0_t5THpoEfYX5_gUWg</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1306897822</pqid></control><display><type>article</type><title>Caveolin-1 plays a crucial role in inhibiting neuronal differentiation of neural stem/progenitor cells via VEGF signaling-dependent pathway</title><source>Public Library of Science (PLoS) Journals Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Li, Yue ; Luo, Jianmin ; Lau, Wui-Man ; Zheng, Guoqing ; Fu, Shuping ; Wang, Ting-Ting ; Zeng, He-Ping ; So, Kwok-Fai ; Chung, Sookja Kim ; Tong, Yao ; Liu, Kejian ; Shen, Jiangang</creator><creatorcontrib>Li, Yue ; Luo, Jianmin ; Lau, Wui-Man ; Zheng, Guoqing ; Fu, Shuping ; Wang, Ting-Ting ; Zeng, He-Ping ; So, Kwok-Fai ; Chung, Sookja Kim ; Tong, Yao ; Liu, Kejian ; Shen, Jiangang</creatorcontrib><description>In 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% O₂ for 24 h and then switched to 21% O₂ for 1, 3, 7 and 14 days whereas normoxic NPCs were continuously cultured with 21% O₂. 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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0022901</identifier><identifier>PMID: 21826216</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>AKT protein ; Animals ; Biology ; Blotting, Western ; Caveolin ; Caveolin 1 - genetics ; Caveolin 1 - metabolism ; Caveolin-1 ; Cell Differentiation - genetics ; Cell Differentiation - physiology ; Cell growth ; Cells (biology) ; Dentate gyrus ; Differentiation ; Embryos ; Enzyme-Linked Immunosorbent Assay ; Hippocampus ; Hypoxia ; Immunohistochemistry ; Invaginations ; Kinases ; Medicine ; Membrane proteins ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neural stem cells ; Neural Stem Cells - cytology ; Neural Stem Cells - metabolism ; Neurons ; Phosphorylation ; Progenitor cells ; Ribonucleic acid ; RNA ; RNA, Small Interfering ; Rodents ; Scaffolding ; Signal transduction ; Signal Transduction - genetics ; Signal Transduction - physiology ; Signaling ; siRNA ; Stat3 protein ; Stem cells ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - metabolism</subject><ispartof>PloS one, 2011-08, Vol.6 (8), p.e22901-e22901</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Li et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-36b3ccde0ed1f85c7ea76dfa6d20f5df51b8ed67e13722cc7adb96de204cfc23</citedby><cites>FETCH-LOGICAL-c691t-36b3ccde0ed1f85c7ea76dfa6d20f5df51b8ed67e13722cc7adb96de204cfc23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149620/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149620/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21826216$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Yue</creatorcontrib><creatorcontrib>Luo, Jianmin</creatorcontrib><creatorcontrib>Lau, Wui-Man</creatorcontrib><creatorcontrib>Zheng, Guoqing</creatorcontrib><creatorcontrib>Fu, Shuping</creatorcontrib><creatorcontrib>Wang, Ting-Ting</creatorcontrib><creatorcontrib>Zeng, He-Ping</creatorcontrib><creatorcontrib>So, Kwok-Fai</creatorcontrib><creatorcontrib>Chung, Sookja Kim</creatorcontrib><creatorcontrib>Tong, Yao</creatorcontrib><creatorcontrib>Liu, Kejian</creatorcontrib><creatorcontrib>Shen, Jiangang</creatorcontrib><title>Caveolin-1 plays a crucial role in inhibiting neuronal differentiation of neural stem/progenitor cells via VEGF signaling-dependent pathway</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In 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% O₂ for 24 h and then switched to 21% O₂ for 1, 3, 7 and 14 days whereas normoxic NPCs were continuously cultured with 21% O₂. 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.</description><subject>AKT protein</subject><subject>Animals</subject><subject>Biology</subject><subject>Blotting, Western</subject><subject>Caveolin</subject><subject>Caveolin 1 - genetics</subject><subject>Caveolin 1 - metabolism</subject><subject>Caveolin-1</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - physiology</subject><subject>Cell growth</subject><subject>Cells (biology)</subject><subject>Dentate gyrus</subject><subject>Differentiation</subject><subject>Embryos</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Hippocampus</subject><subject>Hypoxia</subject><subject>Immunohistochemistry</subject><subject>Invaginations</subject><subject>Kinases</subject><subject>Medicine</subject><subject>Membrane proteins</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Neural stem cells</subject><subject>Neural Stem Cells - cytology</subject><subject>Neural Stem Cells - metabolism</subject><subject>Neurons</subject><subject>Phosphorylation</subject><subject>Progenitor cells</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Small Interfering</subject><subject>Rodents</subject><subject>Scaffolding</subject><subject>Signal transduction</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - physiology</subject><subject>Signaling</subject><subject>siRNA</subject><subject>Stat3 protein</subject><subject>Stem cells</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99q2zAUxs3YWLtubzA2wWBjF0n1x5btm0IpbRcoFLbSWyFLR46KI3mSnS3PsJee3KSlGb0YMkjo_M53rE86Wfae4DlhJTm-82Nwspv33sEcY0prTF5kh6RmdMYpZi-frA-yNzHeYVywivPX2QElFeWU8MPsz5lcg--smxHUd3ITkUQqjMrKDgXfAbIufUvb2MG6FjkYg09VkbbGQAA3WDlY75A397EUiQOsjvvgW3B28AEp6LqI1lai2_PLCxRtm_KT1kxDD04nCdTLYflLbt5mr4zsIrzbzUfZzcX5zdm32dX15eLs9GqmeE2GGeMNU0oDBk1MVagSZMm1kVxTbAptCtJUoHkJySZKlSqlbmqugeJcGUXZUfZxK9t3PoqdjVEQhnlVlxWdiMWW0F7eiT7YlQwb4aUV9xs-tEKGwaoOBJFY1UYxTGqc44Y1TY4lAU5LACkxTlonu2pjswKt0nmTS3ui-xFnl6L1a8FIXk93d5R92QkE_3OEOIiVjZOp0oEfo6gqiquyKKpEfvqHfP5wO6qV6f-tMz6VVZOmOM1LXlWM5UWi5s9QaWhYWZWenLFpfy_h615CYgb4PbRyjFEsfnz_f_b6dp_9_IRdguyGZfTdOL26uA_mW1AFH2MA8-gxwWLqmAc3xNQxYtcxKe3D0_t5THpoEfYX5_gUWg</recordid><startdate>20110803</startdate><enddate>20110803</enddate><creator>Li, Yue</creator><creator>Luo, Jianmin</creator><creator>Lau, Wui-Man</creator><creator>Zheng, Guoqing</creator><creator>Fu, Shuping</creator><creator>Wang, Ting-Ting</creator><creator>Zeng, He-Ping</creator><creator>So, Kwok-Fai</creator><creator>Chung, Sookja Kim</creator><creator>Tong, Yao</creator><creator>Liu, Kejian</creator><creator>Shen, Jiangang</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20110803</creationdate><title>Caveolin-1 plays a crucial role in inhibiting neuronal differentiation of neural stem/progenitor cells via VEGF signaling-dependent pathway</title><author>Li, Yue ; Luo, Jianmin ; Lau, Wui-Man ; Zheng, Guoqing ; Fu, Shuping ; Wang, Ting-Ting ; Zeng, He-Ping ; So, Kwok-Fai ; Chung, Sookja Kim ; Tong, Yao ; Liu, Kejian ; Shen, Jiangang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-36b3ccde0ed1f85c7ea76dfa6d20f5df51b8ed67e13722cc7adb96de204cfc23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>AKT protein</topic><topic>Animals</topic><topic>Biology</topic><topic>Blotting, Western</topic><topic>Caveolin</topic><topic>Caveolin 1 - genetics</topic><topic>Caveolin 1 - metabolism</topic><topic>Caveolin-1</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - physiology</topic><topic>Cell growth</topic><topic>Cells (biology)</topic><topic>Dentate gyrus</topic><topic>Differentiation</topic><topic>Embryos</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Hippocampus</topic><topic>Hypoxia</topic><topic>Immunohistochemistry</topic><topic>Invaginations</topic><topic>Kinases</topic><topic>Medicine</topic><topic>Membrane proteins</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Neural stem cells</topic><topic>Neural Stem Cells - cytology</topic><topic>Neural Stem Cells - metabolism</topic><topic>Neurons</topic><topic>Phosphorylation</topic><topic>Progenitor cells</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Small Interfering</topic><topic>Rodents</topic><topic>Scaffolding</topic><topic>Signal transduction</topic><topic>Signal Transduction - genetics</topic><topic>Signal Transduction - physiology</topic><topic>Signaling</topic><topic>siRNA</topic><topic>Stat3 protein</topic><topic>Stem cells</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Yue</creatorcontrib><creatorcontrib>Luo, Jianmin</creatorcontrib><creatorcontrib>Lau, Wui-Man</creatorcontrib><creatorcontrib>Zheng, Guoqing</creatorcontrib><creatorcontrib>Fu, Shuping</creatorcontrib><creatorcontrib>Wang, Ting-Ting</creatorcontrib><creatorcontrib>Zeng, He-Ping</creatorcontrib><creatorcontrib>So, Kwok-Fai</creatorcontrib><creatorcontrib>Chung, Sookja Kim</creatorcontrib><creatorcontrib>Tong, Yao</creatorcontrib><creatorcontrib>Liu, Kejian</creatorcontrib><creatorcontrib>Shen, Jiangang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Yue</au><au>Luo, Jianmin</au><au>Lau, Wui-Man</au><au>Zheng, Guoqing</au><au>Fu, Shuping</au><au>Wang, Ting-Ting</au><au>Zeng, He-Ping</au><au>So, Kwok-Fai</au><au>Chung, Sookja Kim</au><au>Tong, Yao</au><au>Liu, Kejian</au><au>Shen, Jiangang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Caveolin-1 plays a crucial role in inhibiting neuronal differentiation of neural stem/progenitor cells via VEGF signaling-dependent pathway</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-08-03</date><risdate>2011</risdate><volume>6</volume><issue>8</issue><spage>e22901</spage><epage>e22901</epage><pages>e22901-e22901</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>In 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% O₂ for 24 h and then switched to 21% O₂ for 1, 3, 7 and 14 days whereas normoxic NPCs were continuously cultured with 21% O₂. 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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21826216</pmid><doi>10.1371/journal.pone.0022901</doi><tpages>e22901</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-08, Vol.6 (8), p.e22901-e22901 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1306897822 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | AKT protein Animals Biology Blotting, Western Caveolin Caveolin 1 - genetics Caveolin 1 - metabolism Caveolin-1 Cell Differentiation - genetics Cell Differentiation - physiology Cell growth Cells (biology) Dentate gyrus Differentiation Embryos Enzyme-Linked Immunosorbent Assay Hippocampus Hypoxia Immunohistochemistry Invaginations Kinases Medicine Membrane proteins Mice Mice, Inbred C57BL Mice, Knockout Neural stem cells Neural Stem Cells - cytology Neural Stem Cells - metabolism Neurons Phosphorylation Progenitor cells Ribonucleic acid RNA RNA, Small Interfering Rodents Scaffolding Signal transduction Signal Transduction - genetics Signal Transduction - physiology Signaling siRNA Stat3 protein Stem cells Vascular endothelial growth factor Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - metabolism |
| title | Caveolin-1 plays a crucial role in inhibiting neuronal differentiation of neural stem/progenitor cells via VEGF signaling-dependent pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T05%3A14%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Caveolin-1%20plays%20a%20crucial%20role%20in%20inhibiting%20neuronal%20differentiation%20of%20neural%20stem/progenitor%20cells%20via%20VEGF%20signaling-dependent%20pathway&rft.jtitle=PloS%20one&rft.au=Li,%20Yue&rft.date=2011-08-03&rft.volume=6&rft.issue=8&rft.spage=e22901&rft.epage=e22901&rft.pages=e22901-e22901&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0022901&rft_dat=%3Cgale_plos_%3EA476883345%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1306897822&rft_id=info:pmid/21826216&rft_galeid=A476883345&rft_doaj_id=oai_doaj_org_article_1a0c9fc3019040b3bb40a1e627eeaa00&rfr_iscdi=true |