Astrocytes Regulate Angiogenesis Through the Jagged1-Mediated Notch1 Pathway After Status Epilepticus
Vascular disruptions including blood–brain barrier breakdown and pathologic angiogenesis contribute to the development of epilepsy in normal brains. The Notch signaling pathway is activated in response to seizure activity, and its activation promotes seizures, although its exact role in angiogenesis...
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| Veröffentlicht in: | Molecular neurobiology 2016-11, Vol.53 (9), p.5893-5901 |
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| creator | Zhai, Xuan Liang, Ping Li, Yingliang Li, Lusheng Zhou, Yudong Wu, Xuanxuan Deng, Jinmu Jiang, Li |
| description | Vascular disruptions including blood–brain barrier breakdown and pathologic angiogenesis contribute to the development of epilepsy in normal brains. The Notch signaling pathway is activated in response to seizure activity, and its activation promotes seizures, although its exact role in angiogenesis is poorly understood. Here, we have examined the role of Notch signaling in angiogenesis in a kainic acid-induced mouse model of epilepsy. We show that following seizures, expression of the Notch ligand Jagged1 in the hippocampus is upregulated in astrocytes and levels of activated Notch1 are increased in endothelial cells. Using an in vitro model of angiogenesis, we provide evidence that brain endothelial tube formation is promoted in the presence of astrocytes. Isolated primary brain endothelial cells develop significantly longer vascular sprouts when cultured in the presence of astrocytes. Notch1 signaling is activated in brain endothelial cells cocultured with astrocytes, and astrocytic Jagged1 expression is required for angiogenic enhancement, as shown by the inhibitory effect of Jagged1 small interfering RNA (siRNA) expression in astrocytes on endothelial cell vascular sprouting in vitro. Therapies targeting the Jagged1/Notch1 signaling pathway may therefore be effective in limiting aberrant angiogenesis following status epilepticus. |
| doi_str_mv | 10.1007/s12035-015-9492-8 |
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The Notch signaling pathway is activated in response to seizure activity, and its activation promotes seizures, although its exact role in angiogenesis is poorly understood. Here, we have examined the role of Notch signaling in angiogenesis in a kainic acid-induced mouse model of epilepsy. We show that following seizures, expression of the Notch ligand Jagged1 in the hippocampus is upregulated in astrocytes and levels of activated Notch1 are increased in endothelial cells. Using an in vitro model of angiogenesis, we provide evidence that brain endothelial tube formation is promoted in the presence of astrocytes. Isolated primary brain endothelial cells develop significantly longer vascular sprouts when cultured in the presence of astrocytes. Notch1 signaling is activated in brain endothelial cells cocultured with astrocytes, and astrocytic Jagged1 expression is required for angiogenic enhancement, as shown by the inhibitory effect of Jagged1 small interfering RNA (siRNA) expression in astrocytes on endothelial cell vascular sprouting in vitro. Therapies targeting the Jagged1/Notch1 signaling pathway may therefore be effective in limiting aberrant angiogenesis following status epilepticus.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-015-9492-8</identifier><identifier>PMID: 26507745</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Angiogenesis ; Animals ; Astrocytes - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Brain - metabolism ; Brain - pathology ; Cell Biology ; Coculture Techniques ; Endothelial Cells - metabolism ; Endothelium ; Epilepsy ; Gene Knockdown Techniques ; Jagged-1 Protein - metabolism ; Kainic Acid ; Male ; Mice, Inbred C57BL ; Neovascularization, Physiologic ; Neurobiology ; Neurology ; Neurosciences ; Receptor, Notch1 - metabolism ; Signal Transduction ; Status Epilepticus - metabolism</subject><ispartof>Molecular neurobiology, 2016-11, Vol.53 (9), p.5893-5901</ispartof><rights>Springer Science+Business Media New York 2015</rights><rights>Springer Science+Business Media New York 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-d162f7d717aa130c58e7315c6c2bbc187411b61bde22894ce42e26dc98e99bc23</citedby><cites>FETCH-LOGICAL-c405t-d162f7d717aa130c58e7315c6c2bbc187411b61bde22894ce42e26dc98e99bc23</cites><orcidid>0000-0002-9368-0265</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-015-9492-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-015-9492-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26507745$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhai, Xuan</creatorcontrib><creatorcontrib>Liang, Ping</creatorcontrib><creatorcontrib>Li, Yingliang</creatorcontrib><creatorcontrib>Li, Lusheng</creatorcontrib><creatorcontrib>Zhou, Yudong</creatorcontrib><creatorcontrib>Wu, Xuanxuan</creatorcontrib><creatorcontrib>Deng, Jinmu</creatorcontrib><creatorcontrib>Jiang, Li</creatorcontrib><title>Astrocytes Regulate Angiogenesis Through the Jagged1-Mediated Notch1 Pathway After Status Epilepticus</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><description>Vascular disruptions including blood–brain barrier breakdown and pathologic angiogenesis contribute to the development of epilepsy in normal brains. The Notch signaling pathway is activated in response to seizure activity, and its activation promotes seizures, although its exact role in angiogenesis is poorly understood. Here, we have examined the role of Notch signaling in angiogenesis in a kainic acid-induced mouse model of epilepsy. We show that following seizures, expression of the Notch ligand Jagged1 in the hippocampus is upregulated in astrocytes and levels of activated Notch1 are increased in endothelial cells. Using an in vitro model of angiogenesis, we provide evidence that brain endothelial tube formation is promoted in the presence of astrocytes. Isolated primary brain endothelial cells develop significantly longer vascular sprouts when cultured in the presence of astrocytes. Notch1 signaling is activated in brain endothelial cells cocultured with astrocytes, and astrocytic Jagged1 expression is required for angiogenic enhancement, as shown by the inhibitory effect of Jagged1 small interfering RNA (siRNA) expression in astrocytes on endothelial cell vascular sprouting in vitro. Therapies targeting the Jagged1/Notch1 signaling pathway may therefore be effective in limiting aberrant angiogenesis following status epilepticus.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Astrocytes - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Cell Biology</subject><subject>Coculture Techniques</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium</subject><subject>Epilepsy</subject><subject>Gene Knockdown Techniques</subject><subject>Jagged-1 Protein - metabolism</subject><subject>Kainic Acid</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Neovascularization, Physiologic</subject><subject>Neurobiology</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Receptor, Notch1 - metabolism</subject><subject>Signal Transduction</subject><subject>Status Epilepticus - 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metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>Cell Biology</topic><topic>Coculture Techniques</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelium</topic><topic>Epilepsy</topic><topic>Gene Knockdown Techniques</topic><topic>Jagged-1 Protein - metabolism</topic><topic>Kainic Acid</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>Neovascularization, Physiologic</topic><topic>Neurobiology</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Receptor, Notch1 - metabolism</topic><topic>Signal Transduction</topic><topic>Status Epilepticus - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhai, Xuan</creatorcontrib><creatorcontrib>Liang, Ping</creatorcontrib><creatorcontrib>Li, Yingliang</creatorcontrib><creatorcontrib>Li, Lusheng</creatorcontrib><creatorcontrib>Zhou, Yudong</creatorcontrib><creatorcontrib>Wu, Xuanxuan</creatorcontrib><creatorcontrib>Deng, Jinmu</creatorcontrib><creatorcontrib>Jiang, Li</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhai, Xuan</au><au>Liang, Ping</au><au>Li, Yingliang</au><au>Li, Lusheng</au><au>Zhou, Yudong</au><au>Wu, Xuanxuan</au><au>Deng, Jinmu</au><au>Jiang, Li</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Astrocytes Regulate Angiogenesis Through the Jagged1-Mediated Notch1 Pathway After Status Epilepticus</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><addtitle>Mol Neurobiol</addtitle><date>2016-11-01</date><risdate>2016</risdate><volume>53</volume><issue>9</issue><spage>5893</spage><epage>5901</epage><pages>5893-5901</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><abstract>Vascular disruptions including blood–brain barrier breakdown and pathologic angiogenesis contribute to the development of epilepsy in normal brains. The Notch signaling pathway is activated in response to seizure activity, and its activation promotes seizures, although its exact role in angiogenesis is poorly understood. Here, we have examined the role of Notch signaling in angiogenesis in a kainic acid-induced mouse model of epilepsy. We show that following seizures, expression of the Notch ligand Jagged1 in the hippocampus is upregulated in astrocytes and levels of activated Notch1 are increased in endothelial cells. Using an in vitro model of angiogenesis, we provide evidence that brain endothelial tube formation is promoted in the presence of astrocytes. Isolated primary brain endothelial cells develop significantly longer vascular sprouts when cultured in the presence of astrocytes. Notch1 signaling is activated in brain endothelial cells cocultured with astrocytes, and astrocytic Jagged1 expression is required for angiogenic enhancement, as shown by the inhibitory effect of Jagged1 small interfering RNA (siRNA) expression in astrocytes on endothelial cell vascular sprouting in vitro. Therapies targeting the Jagged1/Notch1 signaling pathway may therefore be effective in limiting aberrant angiogenesis following status epilepticus.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>26507745</pmid><doi>10.1007/s12035-015-9492-8</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-9368-0265</orcidid></addata></record> |
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| subjects | Angiogenesis Animals Astrocytes - metabolism Biomedical and Life Sciences Biomedicine Brain - metabolism Brain - pathology Cell Biology Coculture Techniques Endothelial Cells - metabolism Endothelium Epilepsy Gene Knockdown Techniques Jagged-1 Protein - metabolism Kainic Acid Male Mice, Inbred C57BL Neovascularization, Physiologic Neurobiology Neurology Neurosciences Receptor, Notch1 - metabolism Signal Transduction Status Epilepticus - metabolism |
| title | Astrocytes Regulate Angiogenesis Through the Jagged1-Mediated Notch1 Pathway After Status Epilepticus |
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