Notch1 mediates visfatin-induced FGF-2 up-regulation and endothelial angiogenesis
Our aims were to determine the role of Notch1 in mediating visfatin-induced angiogenesis and to explore potential target genes involved. Inhibition of Notch signalling attenuated visfatin-induced angiogenesis in vitro, ex vivo, and in vivo. Visfatin increased γ-secretase activity, Notch1 cleavage an...
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Veröffentlicht in: | Cardiovascular research 2011-02, Vol.89 (2), p.436-445 |
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creator | BAE, Yun-Hee PARK, Hyun-Joo BAE, Soo-Kyung KIM, Su-Ryun KIM, Jee-Young KANG, Youra KIM, Jung-Ae WEE, Hee-Jun KAGEYAMA, Ryoichiro JIN SUP JUNG BAE, Moon-Kyoung |
description | Our aims were to determine the role of Notch1 in mediating visfatin-induced angiogenesis and to explore potential target genes involved.
Inhibition of Notch signalling attenuated visfatin-induced angiogenesis in vitro, ex vivo, and in vivo. Visfatin increased γ-secretase activity, Notch1 cleavage and activation, and Hes1 gene induction. Visfatin also stimulated fibroblast growth factor-2 (FGF-2) gene expression in a Notch1-dependent manner. Enforced expression of active Notch1 intracellular domain increased FGF-2 protein levels and stimulated endothelial tube formation, whereas blocking Notch1 signalling or knockdown of Notch1 by small interfering RNA suppressed visfatin-induced FGF-2 up-regulation and angiogenesis. Reporter analysis of FGF-2 promoter revealed the presence of CSL (CBF-1, suppressor of hairless, LAG-1)-binding site, and chromatin immunoprecipitation analysis demonstrated the binding of Notch1-CSL complex to this site in response to visfatin.
Our data provide the first example of Notch1-dependent endothelial FGF-2 induction by visfatin and of Notch1 activation in visfatin-stimulated endothelial angiogenesis, suggesting that the signalling axis of visfatin/Notch1/angiogenic factors like FGF-2 might be a valuable target for pathological angiogenesis. |
doi_str_mv | 10.1093/cvr/cvq276 |
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Inhibition of Notch signalling attenuated visfatin-induced angiogenesis in vitro, ex vivo, and in vivo. Visfatin increased γ-secretase activity, Notch1 cleavage and activation, and Hes1 gene induction. Visfatin also stimulated fibroblast growth factor-2 (FGF-2) gene expression in a Notch1-dependent manner. Enforced expression of active Notch1 intracellular domain increased FGF-2 protein levels and stimulated endothelial tube formation, whereas blocking Notch1 signalling or knockdown of Notch1 by small interfering RNA suppressed visfatin-induced FGF-2 up-regulation and angiogenesis. Reporter analysis of FGF-2 promoter revealed the presence of CSL (CBF-1, suppressor of hairless, LAG-1)-binding site, and chromatin immunoprecipitation analysis demonstrated the binding of Notch1-CSL complex to this site in response to visfatin.
Our data provide the first example of Notch1-dependent endothelial FGF-2 induction by visfatin and of Notch1 activation in visfatin-stimulated endothelial angiogenesis, suggesting that the signalling axis of visfatin/Notch1/angiogenic factors like FGF-2 might be a valuable target for pathological angiogenesis.</description><identifier>ISSN: 0008-6363</identifier><identifier>EISSN: 1755-3245</identifier><identifier>DOI: 10.1093/cvr/cvq276</identifier><identifier>PMID: 20817637</identifier><identifier>CODEN: CVREAU</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Amyloid Precursor Protein Secretases - antagonists & inhibitors ; Amyloid Precursor Protein Secretases - metabolism ; Animals ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Binding Sites ; Biological and medical sciences ; Cardiology. Vascular system ; Cells, Cultured ; Chick Embryo ; Chromatin Immunoprecipitation ; Cytokines - metabolism ; Dipeptides - pharmacology ; Endothelial Cells - drug effects ; Endothelial Cells - enzymology ; Enzyme Inhibitors - pharmacology ; Fibroblast Growth Factor 2 - genetics ; Fibroblast Growth Factor 2 - metabolism ; Genes, Reporter ; Homeodomain Proteins - genetics ; Humans ; Immunoglobulin J Recombination Signal Sequence-Binding Protein - metabolism ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Neovascularization, Physiologic - drug effects ; Nicotinamide Phosphoribosyltransferase - metabolism ; Promoter Regions, Genetic ; Rats ; Rats, Sprague-Dawley ; Receptor, Notch1 - genetics ; Receptor, Notch1 - metabolism ; Recombinant Proteins - metabolism ; RNA Interference ; Signal Transduction ; Transcription Factor HES-1 ; Transfection ; Up-Regulation</subject><ispartof>Cardiovascular research, 2011-02, Vol.89 (2), p.436-445</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c352t-cca40637ea1240bf13d90790732358150d5b18c2ad8efd8bedd2b997622b0db43</citedby><cites>FETCH-LOGICAL-c352t-cca40637ea1240bf13d90790732358150d5b18c2ad8efd8bedd2b997622b0db43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23896520$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20817637$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BAE, Yun-Hee</creatorcontrib><creatorcontrib>PARK, Hyun-Joo</creatorcontrib><creatorcontrib>BAE, Soo-Kyung</creatorcontrib><creatorcontrib>KIM, Su-Ryun</creatorcontrib><creatorcontrib>KIM, Jee-Young</creatorcontrib><creatorcontrib>KANG, Youra</creatorcontrib><creatorcontrib>KIM, Jung-Ae</creatorcontrib><creatorcontrib>WEE, Hee-Jun</creatorcontrib><creatorcontrib>KAGEYAMA, Ryoichiro</creatorcontrib><creatorcontrib>JIN SUP JUNG</creatorcontrib><creatorcontrib>BAE, Moon-Kyoung</creatorcontrib><title>Notch1 mediates visfatin-induced FGF-2 up-regulation and endothelial angiogenesis</title><title>Cardiovascular research</title><addtitle>Cardiovasc Res</addtitle><description>Our aims were to determine the role of Notch1 in mediating visfatin-induced angiogenesis and to explore potential target genes involved.
Inhibition of Notch signalling attenuated visfatin-induced angiogenesis in vitro, ex vivo, and in vivo. Visfatin increased γ-secretase activity, Notch1 cleavage and activation, and Hes1 gene induction. Visfatin also stimulated fibroblast growth factor-2 (FGF-2) gene expression in a Notch1-dependent manner. Enforced expression of active Notch1 intracellular domain increased FGF-2 protein levels and stimulated endothelial tube formation, whereas blocking Notch1 signalling or knockdown of Notch1 by small interfering RNA suppressed visfatin-induced FGF-2 up-regulation and angiogenesis. Reporter analysis of FGF-2 promoter revealed the presence of CSL (CBF-1, suppressor of hairless, LAG-1)-binding site, and chromatin immunoprecipitation analysis demonstrated the binding of Notch1-CSL complex to this site in response to visfatin.
Our data provide the first example of Notch1-dependent endothelial FGF-2 induction by visfatin and of Notch1 activation in visfatin-stimulated endothelial angiogenesis, suggesting that the signalling axis of visfatin/Notch1/angiogenic factors like FGF-2 might be a valuable target for pathological angiogenesis.</description><subject>Amyloid Precursor Protein Secretases - antagonists & inhibitors</subject><subject>Amyloid Precursor Protein Secretases - metabolism</subject><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Cardiology. Vascular system</subject><subject>Cells, Cultured</subject><subject>Chick Embryo</subject><subject>Chromatin Immunoprecipitation</subject><subject>Cytokines - metabolism</subject><subject>Dipeptides - pharmacology</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - enzymology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fibroblast Growth Factor 2 - genetics</subject><subject>Fibroblast Growth Factor 2 - metabolism</subject><subject>Genes, Reporter</subject><subject>Homeodomain Proteins - genetics</subject><subject>Humans</subject><subject>Immunoglobulin J Recombination Signal Sequence-Binding Protein - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Nicotinamide Phosphoribosyltransferase - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, Notch1 - genetics</subject><subject>Receptor, Notch1 - metabolism</subject><subject>Recombinant Proteins - metabolism</subject><subject>RNA Interference</subject><subject>Signal Transduction</subject><subject>Transcription Factor HES-1</subject><subject>Transfection</subject><subject>Up-Regulation</subject><issn>0008-6363</issn><issn>1755-3245</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkG9LwzAQh4Mobk7f-AGkb0QQovnTNOlLGW4KQxH0dUmT6xbp0i1pB357I5sKdxw_7uE4HoQuKbmjpOT3ZhdSb5ksjtCYSiEwZ7k4RmNCiMIFL_gIncX4maIQMj9FI0YUlQWXY_T20vVmRbM1WKd7iNnOxUb3zmPn7WDAZrP5DLNs2OAAy6FNq85n2tsMvO36FbROtykvXbcED9HFc3TS6DbCxWFO0Mfs8X36hBev8-fpwwIbLliPjdE5SS-ApiwndUO5LYlMxRkXigpiRU2VYdoqaKyqwVpWl6UsGKuJrXM-QTf7u5vQbQeIfbV20UDbag_dECuVE54rWchE3u5JE7oYAzTVJri1Dl8VJdWPwSoZrPYGE3x1ODvUScof-qssAdcHQEej2yZob1z857gqC8EI_wakUHna</recordid><startdate>20110201</startdate><enddate>20110201</enddate><creator>BAE, Yun-Hee</creator><creator>PARK, Hyun-Joo</creator><creator>BAE, Soo-Kyung</creator><creator>KIM, Su-Ryun</creator><creator>KIM, Jee-Young</creator><creator>KANG, Youra</creator><creator>KIM, Jung-Ae</creator><creator>WEE, Hee-Jun</creator><creator>KAGEYAMA, Ryoichiro</creator><creator>JIN SUP JUNG</creator><creator>BAE, Moon-Kyoung</creator><general>Oxford University Press</general><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20110201</creationdate><title>Notch1 mediates visfatin-induced FGF-2 up-regulation and endothelial angiogenesis</title><author>BAE, Yun-Hee ; PARK, Hyun-Joo ; BAE, Soo-Kyung ; KIM, Su-Ryun ; KIM, Jee-Young ; KANG, Youra ; KIM, Jung-Ae ; WEE, Hee-Jun ; KAGEYAMA, Ryoichiro ; JIN SUP JUNG ; BAE, Moon-Kyoung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c352t-cca40637ea1240bf13d90790732358150d5b18c2ad8efd8bedd2b997622b0db43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Amyloid Precursor Protein Secretases - antagonists & inhibitors</topic><topic>Amyloid Precursor Protein Secretases - metabolism</topic><topic>Animals</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Cardiology. Vascular system</topic><topic>Cells, Cultured</topic><topic>Chick Embryo</topic><topic>Chromatin Immunoprecipitation</topic><topic>Cytokines - metabolism</topic><topic>Dipeptides - pharmacology</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - enzymology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fibroblast Growth Factor 2 - genetics</topic><topic>Fibroblast Growth Factor 2 - metabolism</topic><topic>Genes, Reporter</topic><topic>Homeodomain Proteins - genetics</topic><topic>Humans</topic><topic>Immunoglobulin J Recombination Signal Sequence-Binding Protein - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Nicotinamide Phosphoribosyltransferase - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, Notch1 - genetics</topic><topic>Receptor, Notch1 - metabolism</topic><topic>Recombinant Proteins - metabolism</topic><topic>RNA Interference</topic><topic>Signal Transduction</topic><topic>Transcription Factor HES-1</topic><topic>Transfection</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BAE, Yun-Hee</creatorcontrib><creatorcontrib>PARK, Hyun-Joo</creatorcontrib><creatorcontrib>BAE, Soo-Kyung</creatorcontrib><creatorcontrib>KIM, Su-Ryun</creatorcontrib><creatorcontrib>KIM, Jee-Young</creatorcontrib><creatorcontrib>KANG, Youra</creatorcontrib><creatorcontrib>KIM, Jung-Ae</creatorcontrib><creatorcontrib>WEE, Hee-Jun</creatorcontrib><creatorcontrib>KAGEYAMA, Ryoichiro</creatorcontrib><creatorcontrib>JIN SUP JUNG</creatorcontrib><creatorcontrib>BAE, Moon-Kyoung</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cardiovascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BAE, Yun-Hee</au><au>PARK, Hyun-Joo</au><au>BAE, Soo-Kyung</au><au>KIM, Su-Ryun</au><au>KIM, Jee-Young</au><au>KANG, Youra</au><au>KIM, Jung-Ae</au><au>WEE, Hee-Jun</au><au>KAGEYAMA, Ryoichiro</au><au>JIN SUP JUNG</au><au>BAE, Moon-Kyoung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Notch1 mediates visfatin-induced FGF-2 up-regulation and endothelial angiogenesis</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>2011-02-01</date><risdate>2011</risdate><volume>89</volume><issue>2</issue><spage>436</spage><epage>445</epage><pages>436-445</pages><issn>0008-6363</issn><eissn>1755-3245</eissn><coden>CVREAU</coden><abstract>Our aims were to determine the role of Notch1 in mediating visfatin-induced angiogenesis and to explore potential target genes involved.
Inhibition of Notch signalling attenuated visfatin-induced angiogenesis in vitro, ex vivo, and in vivo. Visfatin increased γ-secretase activity, Notch1 cleavage and activation, and Hes1 gene induction. Visfatin also stimulated fibroblast growth factor-2 (FGF-2) gene expression in a Notch1-dependent manner. Enforced expression of active Notch1 intracellular domain increased FGF-2 protein levels and stimulated endothelial tube formation, whereas blocking Notch1 signalling or knockdown of Notch1 by small interfering RNA suppressed visfatin-induced FGF-2 up-regulation and angiogenesis. Reporter analysis of FGF-2 promoter revealed the presence of CSL (CBF-1, suppressor of hairless, LAG-1)-binding site, and chromatin immunoprecipitation analysis demonstrated the binding of Notch1-CSL complex to this site in response to visfatin.
Our data provide the first example of Notch1-dependent endothelial FGF-2 induction by visfatin and of Notch1 activation in visfatin-stimulated endothelial angiogenesis, suggesting that the signalling axis of visfatin/Notch1/angiogenic factors like FGF-2 might be a valuable target for pathological angiogenesis.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>20817637</pmid><doi>10.1093/cvr/cvq276</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
subjects | Amyloid Precursor Protein Secretases - antagonists & inhibitors Amyloid Precursor Protein Secretases - metabolism Animals Basic Helix-Loop-Helix Transcription Factors - genetics Binding Sites Biological and medical sciences Cardiology. Vascular system Cells, Cultured Chick Embryo Chromatin Immunoprecipitation Cytokines - metabolism Dipeptides - pharmacology Endothelial Cells - drug effects Endothelial Cells - enzymology Enzyme Inhibitors - pharmacology Fibroblast Growth Factor 2 - genetics Fibroblast Growth Factor 2 - metabolism Genes, Reporter Homeodomain Proteins - genetics Humans Immunoglobulin J Recombination Signal Sequence-Binding Protein - metabolism Male Medical sciences Mice Mice, Inbred C57BL Neovascularization, Physiologic - drug effects Nicotinamide Phosphoribosyltransferase - metabolism Promoter Regions, Genetic Rats Rats, Sprague-Dawley Receptor, Notch1 - genetics Receptor, Notch1 - metabolism Recombinant Proteins - metabolism RNA Interference Signal Transduction Transcription Factor HES-1 Transfection Up-Regulation |
title | Notch1 mediates visfatin-induced FGF-2 up-regulation and endothelial angiogenesis |
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