Transcriptional regulation of FGF-2 gene expression in cardiac myocytes
Fibroblast growth factor-2 (FGF-2) exerts its cardioprotective effect through cell surface receptor signaling and may play a role in the normal maintenance of a healthy myocardium. One mechanism of FGF-2 release from contracting cardiomyocytes is through transient sarcolemmal disruption, with accumu...
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| Veröffentlicht in: | Cardiovascular research 2004-06, Vol.62 (3), p.548-557 |
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| description | Fibroblast growth factor-2 (FGF-2) exerts its cardioprotective effect through cell surface receptor signaling and may play a role in the normal maintenance of a healthy myocardium. One mechanism of FGF-2 release from contracting cardiomyocytes is through transient sarcolemmal disruption, with accumulation in the extracellular matrix. Continuous FGF-2 release would require a link to synthesis and, thus, we examined regulation of FGF-2 promoter activity in cardiomyocytes as a potential target for optimizing cardioprotection.
To investigate autoregulation, neonatal rat cardiomyocytes, (NRCM), were transfected with approximately 1 or 0.1 kb of rat FGF-2 promoter sequences linked to luciferase, -1058FGF-2p.luc and -110FGF-2p.luc, and treated with or without FGF-2. FGF-2 promoter activity was significantly increased approximately 2.5-fold with both genes. The proximal promoter region of rat FGF-2 contains putative binding sites for the early growth response-1 (Egr-1) and stimulating protein 1 (Sp1) transcription factors. Overexpression of Egr-1 and Sp1 increased -1058FGF-2p.luc expression by 4.4- and 8.7-fold, respectively. Mutation of Egr-1 and overlapping Sp1 sites did not blunt the response of -110FGF-2p.luc to FGF-2 treatment but did significantly reduce basal promoter activity. Transgenic mice expressing -1058FGF-2p.luc were treated with isoproterenol (IsP) to increase heart rate and endogenous FGF-2 release. FGF-2 promoter activity was stimulated significantly at 6 h, and increases in both FGF-2 and its receptor mRNA levels were also detected. In contrast, no effect of IsP was seen on -1058FGF-2p.luc or -110FGF-2p.luc in transfected NRCMs.
FGF-2 released from cardiomyocytes may act to regulate its own synthesis at the transcriptional level. The mechanism does not appear to require an intact Egr-1 site in the proximal promoter region. This may, however, reflect redundancy in the control of FGF-2 promoter activity as our data support a stimulatory role for Egr-1 and Sp1. |
| doi_str_mv | 10.1016/j.cardiores.2004.01.032 |
| format | Article |
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To investigate autoregulation, neonatal rat cardiomyocytes, (NRCM), were transfected with approximately 1 or 0.1 kb of rat FGF-2 promoter sequences linked to luciferase, -1058FGF-2p.luc and -110FGF-2p.luc, and treated with or without FGF-2. FGF-2 promoter activity was significantly increased approximately 2.5-fold with both genes. The proximal promoter region of rat FGF-2 contains putative binding sites for the early growth response-1 (Egr-1) and stimulating protein 1 (Sp1) transcription factors. Overexpression of Egr-1 and Sp1 increased -1058FGF-2p.luc expression by 4.4- and 8.7-fold, respectively. Mutation of Egr-1 and overlapping Sp1 sites did not blunt the response of -110FGF-2p.luc to FGF-2 treatment but did significantly reduce basal promoter activity. Transgenic mice expressing -1058FGF-2p.luc were treated with isoproterenol (IsP) to increase heart rate and endogenous FGF-2 release. FGF-2 promoter activity was stimulated significantly at 6 h, and increases in both FGF-2 and its receptor mRNA levels were also detected. In contrast, no effect of IsP was seen on -1058FGF-2p.luc or -110FGF-2p.luc in transfected NRCMs.
FGF-2 released from cardiomyocytes may act to regulate its own synthesis at the transcriptional level. The mechanism does not appear to require an intact Egr-1 site in the proximal promoter region. This may, however, reflect redundancy in the control of FGF-2 promoter activity as our data support a stimulatory role for Egr-1 and Sp1.</description><identifier>ISSN: 0008-6363</identifier><identifier>EISSN: 1755-3245</identifier><identifier>DOI: 10.1016/j.cardiores.2004.01.032</identifier><identifier>PMID: 15158147</identifier><identifier>CODEN: CVREAU</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adrenergic beta-Agonists - pharmacology ; Animals ; Biological and medical sciences ; Cardiology. Vascular system ; Cells, Cultured ; Electrophoretic Mobility Shift Assay ; Fibroblast Growth Factor 2 - genetics ; Fibroblast Growth Factor 2 - pharmacology ; Gene Expression Regulation ; Isoproterenol - pharmacology ; Medical sciences ; Mice ; Mice, Transgenic ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - metabolism ; Promoter Regions, Genetic ; Rats ; Receptor Protein-Tyrosine Kinases - analysis ; Receptor, Fibroblast Growth Factor, Type 1 ; Receptors, Fibroblast Growth Factor - analysis ; Transcription, Genetic</subject><ispartof>Cardiovascular research, 2004-06, Vol.62 (3), p.548-557</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-4f997981428583457740bd35393ed9f5930eb24b18742a4bced431695a1d0c8f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15760737$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15158147$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>JIMENEZ, Sarah K</creatorcontrib><creatorcontrib>SHEIKH, Farah</creatorcontrib><creatorcontrib>YAN JIN</creatorcontrib><creatorcontrib>DETILLIEUX, Karen A</creatorcontrib><creatorcontrib>DHALIWAL, Jamit</creatorcontrib><creatorcontrib>KARDAMI, Elissavet</creatorcontrib><creatorcontrib>CATTINI, Peter A</creatorcontrib><title>Transcriptional regulation of FGF-2 gene expression in cardiac myocytes</title><title>Cardiovascular research</title><addtitle>Cardiovasc Res</addtitle><description>Fibroblast growth factor-2 (FGF-2) exerts its cardioprotective effect through cell surface receptor signaling and may play a role in the normal maintenance of a healthy myocardium. One mechanism of FGF-2 release from contracting cardiomyocytes is through transient sarcolemmal disruption, with accumulation in the extracellular matrix. Continuous FGF-2 release would require a link to synthesis and, thus, we examined regulation of FGF-2 promoter activity in cardiomyocytes as a potential target for optimizing cardioprotection.
To investigate autoregulation, neonatal rat cardiomyocytes, (NRCM), were transfected with approximately 1 or 0.1 kb of rat FGF-2 promoter sequences linked to luciferase, -1058FGF-2p.luc and -110FGF-2p.luc, and treated with or without FGF-2. FGF-2 promoter activity was significantly increased approximately 2.5-fold with both genes. The proximal promoter region of rat FGF-2 contains putative binding sites for the early growth response-1 (Egr-1) and stimulating protein 1 (Sp1) transcription factors. Overexpression of Egr-1 and Sp1 increased -1058FGF-2p.luc expression by 4.4- and 8.7-fold, respectively. Mutation of Egr-1 and overlapping Sp1 sites did not blunt the response of -110FGF-2p.luc to FGF-2 treatment but did significantly reduce basal promoter activity. Transgenic mice expressing -1058FGF-2p.luc were treated with isoproterenol (IsP) to increase heart rate and endogenous FGF-2 release. FGF-2 promoter activity was stimulated significantly at 6 h, and increases in both FGF-2 and its receptor mRNA levels were also detected. In contrast, no effect of IsP was seen on -1058FGF-2p.luc or -110FGF-2p.luc in transfected NRCMs.
FGF-2 released from cardiomyocytes may act to regulate its own synthesis at the transcriptional level. The mechanism does not appear to require an intact Egr-1 site in the proximal promoter region. This may, however, reflect redundancy in the control of FGF-2 promoter activity as our data support a stimulatory role for Egr-1 and Sp1.</description><subject>Adrenergic beta-Agonists - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cardiology. Vascular system</subject><subject>Cells, Cultured</subject><subject>Electrophoretic Mobility Shift Assay</subject><subject>Fibroblast Growth Factor 2 - genetics</subject><subject>Fibroblast Growth Factor 2 - pharmacology</subject><subject>Gene Expression Regulation</subject><subject>Isoproterenol - pharmacology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Rats</subject><subject>Receptor Protein-Tyrosine Kinases - analysis</subject><subject>Receptor, Fibroblast Growth Factor, Type 1</subject><subject>Receptors, Fibroblast Growth Factor - analysis</subject><subject>Transcription, Genetic</subject><issn>0008-6363</issn><issn>1755-3245</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkE1Lw0AQhhdRbK3-Bc1Fb4n7mc0eRWwVCl7qedlsJiUlX-4mYP-9GxvU0zDM884LD0J3BCcEk_TxkFjjiqpz4BOKMU8wSTCjZ2hJpBAxo1ycoyXGOItTlrIFuvL-EFYhJL9ECyKIyAiXS7TZOdN666p-qLrW1JGD_VibaYm6Mlpv1jGN9tBCBF99aPPToWqjn3pjo-bY2eMA_hpdlKb2cDPPFfpYv-yeX-Pt--bt-WkbWy74EPNSKalCNc1ExriQkuO8YIIpBoUqhWIYcspzkklODc8tFJyRVAlDCmyzkq3Qw-lv77rPEfygm8pbqGvTQjd6LYkSnBIVQHkCreu8d1Dq3lWNcUdNsJ4c6oP-dagnhxoTHRyG5O1cMeYNFH-5WVoA7mfAeGvqMhi0lf_HyRRLJtk3ywJ8QQ</recordid><startdate>20040601</startdate><enddate>20040601</enddate><creator>JIMENEZ, Sarah K</creator><creator>SHEIKH, Farah</creator><creator>YAN JIN</creator><creator>DETILLIEUX, Karen A</creator><creator>DHALIWAL, Jamit</creator><creator>KARDAMI, Elissavet</creator><creator>CATTINI, Peter A</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>20040601</creationdate><title>Transcriptional regulation of FGF-2 gene expression in cardiac myocytes</title><author>JIMENEZ, Sarah K ; SHEIKH, Farah ; YAN JIN ; DETILLIEUX, Karen A ; DHALIWAL, Jamit ; KARDAMI, Elissavet ; CATTINI, Peter A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-4f997981428583457740bd35393ed9f5930eb24b18742a4bced431695a1d0c8f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adrenergic beta-Agonists - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cardiology. Vascular system</topic><topic>Cells, Cultured</topic><topic>Electrophoretic Mobility Shift Assay</topic><topic>Fibroblast Growth Factor 2 - genetics</topic><topic>Fibroblast Growth Factor 2 - pharmacology</topic><topic>Gene Expression Regulation</topic><topic>Isoproterenol - pharmacology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Rats</topic><topic>Receptor Protein-Tyrosine Kinases - analysis</topic><topic>Receptor, Fibroblast Growth Factor, Type 1</topic><topic>Receptors, Fibroblast Growth Factor - analysis</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JIMENEZ, Sarah K</creatorcontrib><creatorcontrib>SHEIKH, Farah</creatorcontrib><creatorcontrib>YAN JIN</creatorcontrib><creatorcontrib>DETILLIEUX, Karen A</creatorcontrib><creatorcontrib>DHALIWAL, Jamit</creatorcontrib><creatorcontrib>KARDAMI, Elissavet</creatorcontrib><creatorcontrib>CATTINI, Peter A</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>JIMENEZ, Sarah K</au><au>SHEIKH, Farah</au><au>YAN JIN</au><au>DETILLIEUX, Karen A</au><au>DHALIWAL, Jamit</au><au>KARDAMI, Elissavet</au><au>CATTINI, Peter A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptional regulation of FGF-2 gene expression in cardiac myocytes</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>2004-06-01</date><risdate>2004</risdate><volume>62</volume><issue>3</issue><spage>548</spage><epage>557</epage><pages>548-557</pages><issn>0008-6363</issn><eissn>1755-3245</eissn><coden>CVREAU</coden><abstract>Fibroblast growth factor-2 (FGF-2) exerts its cardioprotective effect through cell surface receptor signaling and may play a role in the normal maintenance of a healthy myocardium. One mechanism of FGF-2 release from contracting cardiomyocytes is through transient sarcolemmal disruption, with accumulation in the extracellular matrix. Continuous FGF-2 release would require a link to synthesis and, thus, we examined regulation of FGF-2 promoter activity in cardiomyocytes as a potential target for optimizing cardioprotection.
To investigate autoregulation, neonatal rat cardiomyocytes, (NRCM), were transfected with approximately 1 or 0.1 kb of rat FGF-2 promoter sequences linked to luciferase, -1058FGF-2p.luc and -110FGF-2p.luc, and treated with or without FGF-2. FGF-2 promoter activity was significantly increased approximately 2.5-fold with both genes. The proximal promoter region of rat FGF-2 contains putative binding sites for the early growth response-1 (Egr-1) and stimulating protein 1 (Sp1) transcription factors. Overexpression of Egr-1 and Sp1 increased -1058FGF-2p.luc expression by 4.4- and 8.7-fold, respectively. Mutation of Egr-1 and overlapping Sp1 sites did not blunt the response of -110FGF-2p.luc to FGF-2 treatment but did significantly reduce basal promoter activity. Transgenic mice expressing -1058FGF-2p.luc were treated with isoproterenol (IsP) to increase heart rate and endogenous FGF-2 release. FGF-2 promoter activity was stimulated significantly at 6 h, and increases in both FGF-2 and its receptor mRNA levels were also detected. In contrast, no effect of IsP was seen on -1058FGF-2p.luc or -110FGF-2p.luc in transfected NRCMs.
FGF-2 released from cardiomyocytes may act to regulate its own synthesis at the transcriptional level. The mechanism does not appear to require an intact Egr-1 site in the proximal promoter region. This may, however, reflect redundancy in the control of FGF-2 promoter activity as our data support a stimulatory role for Egr-1 and Sp1.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>15158147</pmid><doi>10.1016/j.cardiores.2004.01.032</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adrenergic beta-Agonists - pharmacology Animals Biological and medical sciences Cardiology. Vascular system Cells, Cultured Electrophoretic Mobility Shift Assay Fibroblast Growth Factor 2 - genetics Fibroblast Growth Factor 2 - pharmacology Gene Expression Regulation Isoproterenol - pharmacology Medical sciences Mice Mice, Transgenic Myocytes, Cardiac - drug effects Myocytes, Cardiac - metabolism Promoter Regions, Genetic Rats Receptor Protein-Tyrosine Kinases - analysis Receptor, Fibroblast Growth Factor, Type 1 Receptors, Fibroblast Growth Factor - analysis Transcription, Genetic |
| title | Transcriptional regulation of FGF-2 gene expression in cardiac myocytes |
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