Thrombin selectively induces transcription of genes in human monocytes involved in inflammation and wound healing
Summary Thrombin is essential for blood coagulation but functions also as a mediator of cellular signalling. Gene expression microarray experiments in human monocytes revealed thrombin-induced upregulation of a limited subset of genes, which are almost exclusively involved in inflammation and wound...
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| Veröffentlicht in: | Thrombosis and haemostasis 2014-11, Vol.111 (11), p.992-1001 |
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| container_title | Thrombosis and haemostasis |
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| creator | Lopéz, Mercedes L. Bruges, Gustavo Crespo, Gustavo Salazar, Victor Deglesne, Pierre-Antoine Schneider, Heike Cabrera-Fuentes, Hector Schmitz, M. Lienhard Preissner, Klaus T. |
| description | Summary
Thrombin is essential for blood coagulation but functions also as a mediator of cellular signalling. Gene expression microarray experiments in human monocytes revealed thrombin-induced upregulation of a limited subset of genes, which are almost exclusively involved in inflammation and wound healing. Among these, the expression of F3 gene encoding for tissue factor (TF) was enhanced indicating that this physiological initiator of coagulation cascade may create a feed-forward loop to enhance blood coagulation. Activation of protease-activated receptor type 1 (PAR1) was shown to play a main role in promoting TF expression. Moreover, thrombin induced phosphorylation of ERK1/2, an event that is required for expression of thrombin-regulated genes. Thrombin also increased the expression of TF at the protein level in monocytes as evidenced by Western blot and immunostaining. Furthermore, FXa generation induced by thrombin-stimulated monocytes was abolished by a TF blocking antibody and therefore it is entirely attributable to the expression of tissue factor. This cellular activity of thrombin provides a new molecular link between coagulation, inflammation and wound healing. |
| doi_str_mv | 10.1160/th14-01-0034 |
| format | Article |
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Thrombin is essential for blood coagulation but functions also as a mediator of cellular signalling. Gene expression microarray experiments in human monocytes revealed thrombin-induced upregulation of a limited subset of genes, which are almost exclusively involved in inflammation and wound healing. Among these, the expression of F3 gene encoding for tissue factor (TF) was enhanced indicating that this physiological initiator of coagulation cascade may create a feed-forward loop to enhance blood coagulation. Activation of protease-activated receptor type 1 (PAR1) was shown to play a main role in promoting TF expression. Moreover, thrombin induced phosphorylation of ERK1/2, an event that is required for expression of thrombin-regulated genes. Thrombin also increased the expression of TF at the protein level in monocytes as evidenced by Western blot and immunostaining. Furthermore, FXa generation induced by thrombin-stimulated monocytes was abolished by a TF blocking antibody and therefore it is entirely attributable to the expression of tissue factor. This cellular activity of thrombin provides a new molecular link between coagulation, inflammation and wound healing.</description><identifier>ISSN: 0340-6245</identifier><identifier>EISSN: 2567-689X</identifier><identifier>DOI: 10.1160/th14-01-0034</identifier><identifier>PMID: 25057055</identifier><identifier>CODEN: THHADQ</identifier><language>eng</language><publisher>Stuttgart: Schattauer GmbH</publisher><subject>Blood Coagulation - genetics ; Cells, Cultured ; Factor Xa - biosynthesis ; Feedback, Physiological ; Gene Expression Regulation - drug effects ; Humans ; Inflammation - genetics ; MAP Kinase Signaling System - drug effects ; MAP Kinase Signaling System - physiology ; Monocytes - drug effects ; Monocytes - metabolism ; Oligonucleotide Array Sequence Analysis ; Real-Time Polymerase Chain Reaction ; Receptor, PAR-1 - physiology ; Thrombin - pharmacology ; Thromboplastin - biosynthesis ; Thromboplastin - genetics ; Transcription, Genetic - drug effects ; Up-Regulation - drug effects ; Wound Healing - genetics ; Wound Healing and Inflammation/Infection</subject><ispartof>Thrombosis and haemostasis, 2014-11, Vol.111 (11), p.992-1001</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-633089e418fe999569d01edc267a0d09d074a3057649738aa594fc4bafbdcc753</citedby><cites>FETCH-LOGICAL-c400t-633089e418fe999569d01edc267a0d09d074a3057649738aa594fc4bafbdcc753</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.thieme-connect.de/products/ejournals/pdf/10.1160/th14-01-0034.pdf$$EPDF$$P50$$Gthieme$$H</linktopdf><linktohtml>$$Uhttps://www.thieme-connect.de/products/ejournals/html/10.1160/th14-01-0034$$EHTML$$P50$$Gthieme$$H</linktohtml><link.rule.ids>314,776,780,3005,27901,27902,54534,54535</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28962223$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25057055$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lopéz, Mercedes L.</creatorcontrib><creatorcontrib>Bruges, Gustavo</creatorcontrib><creatorcontrib>Crespo, Gustavo</creatorcontrib><creatorcontrib>Salazar, Victor</creatorcontrib><creatorcontrib>Deglesne, Pierre-Antoine</creatorcontrib><creatorcontrib>Schneider, Heike</creatorcontrib><creatorcontrib>Cabrera-Fuentes, Hector</creatorcontrib><creatorcontrib>Schmitz, M. Lienhard</creatorcontrib><creatorcontrib>Preissner, Klaus T.</creatorcontrib><title>Thrombin selectively induces transcription of genes in human monocytes involved in inflammation and wound healing</title><title>Thrombosis and haemostasis</title><addtitle>Thromb Haemost</addtitle><description>Summary
Thrombin is essential for blood coagulation but functions also as a mediator of cellular signalling. Gene expression microarray experiments in human monocytes revealed thrombin-induced upregulation of a limited subset of genes, which are almost exclusively involved in inflammation and wound healing. Among these, the expression of F3 gene encoding for tissue factor (TF) was enhanced indicating that this physiological initiator of coagulation cascade may create a feed-forward loop to enhance blood coagulation. Activation of protease-activated receptor type 1 (PAR1) was shown to play a main role in promoting TF expression. Moreover, thrombin induced phosphorylation of ERK1/2, an event that is required for expression of thrombin-regulated genes. Thrombin also increased the expression of TF at the protein level in monocytes as evidenced by Western blot and immunostaining. Furthermore, FXa generation induced by thrombin-stimulated monocytes was abolished by a TF blocking antibody and therefore it is entirely attributable to the expression of tissue factor. This cellular activity of thrombin provides a new molecular link between coagulation, inflammation and wound healing.</description><subject>Blood Coagulation - genetics</subject><subject>Cells, Cultured</subject><subject>Factor Xa - biosynthesis</subject><subject>Feedback, Physiological</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Humans</subject><subject>Inflammation - genetics</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAP Kinase Signaling System - physiology</subject><subject>Monocytes - drug effects</subject><subject>Monocytes - metabolism</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptor, PAR-1 - physiology</subject><subject>Thrombin - pharmacology</subject><subject>Thromboplastin - biosynthesis</subject><subject>Thromboplastin - genetics</subject><subject>Transcription, Genetic - drug effects</subject><subject>Up-Regulation - drug effects</subject><subject>Wound Healing - genetics</subject><subject>Wound Healing and Inflammation/Infection</subject><issn>0340-6245</issn><issn>2567-689X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkM9PwyAYhonRuDm9eTa9eNLqRwu0HM3ir2SJl5l4axjQlaWFWdqZ_ffSberFC4SXh4-8D0KXGO4wZnDfVZjEgGOAlByhcUJZFrOcfxyjcUggZgmhI3Tm_QoAM8LpKRolFGgGlI7R57xqXbMwNvK61rIzG11vI2NVL7WPulZYL1uz7oyzkSujpbYhDnTVN8JGjbNObrtdtHH1RqvhztiyFk0jdo-EVdGX68NaaVEbuzxHJ6Wovb447BP0_vQ4n77Es7fn1-nDLJYEoItZmkLONcF5qTnnlHEFWCuZsEyAgnDKiEhDjVApS3MhKCelJAtRLpSUGU0n6HY_V7bO-1aXxbo1jWi3BYZiMFcM5grAxWAu4Fd7fN0vGq1-4R9VAbg-AMJLUZdBjTT-j8s5S5IkDdzNnusqoxtdrFzf2lD0_2-_Abk8hlU</recordid><startdate>20141101</startdate><enddate>20141101</enddate><creator>Lopéz, Mercedes L.</creator><creator>Bruges, Gustavo</creator><creator>Crespo, Gustavo</creator><creator>Salazar, Victor</creator><creator>Deglesne, Pierre-Antoine</creator><creator>Schneider, Heike</creator><creator>Cabrera-Fuentes, Hector</creator><creator>Schmitz, M. Lienhard</creator><creator>Preissner, Klaus T.</creator><general>Schattauer GmbH</general><general>Schattauer</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></search><sort><creationdate>20141101</creationdate><title>Thrombin selectively induces transcription of genes in human monocytes involved in inflammation and wound healing</title><author>Lopéz, Mercedes L. ; Bruges, Gustavo ; Crespo, Gustavo ; Salazar, Victor ; Deglesne, Pierre-Antoine ; Schneider, Heike ; Cabrera-Fuentes, Hector ; Schmitz, M. Lienhard ; Preissner, Klaus T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-633089e418fe999569d01edc267a0d09d074a3057649738aa594fc4bafbdcc753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Blood Coagulation - genetics</topic><topic>Cells, Cultured</topic><topic>Factor Xa - biosynthesis</topic><topic>Feedback, Physiological</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Humans</topic><topic>Inflammation - genetics</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>MAP Kinase Signaling System - physiology</topic><topic>Monocytes - drug effects</topic><topic>Monocytes - metabolism</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptor, PAR-1 - physiology</topic><topic>Thrombin - pharmacology</topic><topic>Thromboplastin - biosynthesis</topic><topic>Thromboplastin - genetics</topic><topic>Transcription, Genetic - drug effects</topic><topic>Up-Regulation - drug effects</topic><topic>Wound Healing - genetics</topic><topic>Wound Healing and Inflammation/Infection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lopéz, Mercedes L.</creatorcontrib><creatorcontrib>Bruges, Gustavo</creatorcontrib><creatorcontrib>Crespo, Gustavo</creatorcontrib><creatorcontrib>Salazar, Victor</creatorcontrib><creatorcontrib>Deglesne, Pierre-Antoine</creatorcontrib><creatorcontrib>Schneider, Heike</creatorcontrib><creatorcontrib>Cabrera-Fuentes, Hector</creatorcontrib><creatorcontrib>Schmitz, M. Lienhard</creatorcontrib><creatorcontrib>Preissner, Klaus T.</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><jtitle>Thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lopéz, Mercedes L.</au><au>Bruges, Gustavo</au><au>Crespo, Gustavo</au><au>Salazar, Victor</au><au>Deglesne, Pierre-Antoine</au><au>Schneider, Heike</au><au>Cabrera-Fuentes, Hector</au><au>Schmitz, M. Lienhard</au><au>Preissner, Klaus T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thrombin selectively induces transcription of genes in human monocytes involved in inflammation and wound healing</atitle><jtitle>Thrombosis and haemostasis</jtitle><addtitle>Thromb Haemost</addtitle><date>2014-11-01</date><risdate>2014</risdate><volume>111</volume><issue>11</issue><spage>992</spage><epage>1001</epage><pages>992-1001</pages><issn>0340-6245</issn><eissn>2567-689X</eissn><coden>THHADQ</coden><abstract>Summary
Thrombin is essential for blood coagulation but functions also as a mediator of cellular signalling. Gene expression microarray experiments in human monocytes revealed thrombin-induced upregulation of a limited subset of genes, which are almost exclusively involved in inflammation and wound healing. Among these, the expression of F3 gene encoding for tissue factor (TF) was enhanced indicating that this physiological initiator of coagulation cascade may create a feed-forward loop to enhance blood coagulation. Activation of protease-activated receptor type 1 (PAR1) was shown to play a main role in promoting TF expression. Moreover, thrombin induced phosphorylation of ERK1/2, an event that is required for expression of thrombin-regulated genes. Thrombin also increased the expression of TF at the protein level in monocytes as evidenced by Western blot and immunostaining. Furthermore, FXa generation induced by thrombin-stimulated monocytes was abolished by a TF blocking antibody and therefore it is entirely attributable to the expression of tissue factor. This cellular activity of thrombin provides a new molecular link between coagulation, inflammation and wound healing.</abstract><cop>Stuttgart</cop><pub>Schattauer GmbH</pub><pmid>25057055</pmid><doi>10.1160/th14-01-0034</doi><tpages>10</tpages></addata></record> |
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| ispartof | Thrombosis and haemostasis, 2014-11, Vol.111 (11), p.992-1001 |
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| source | MEDLINE; Thieme Connect Journals |
| subjects | Blood Coagulation - genetics Cells, Cultured Factor Xa - biosynthesis Feedback, Physiological Gene Expression Regulation - drug effects Humans Inflammation - genetics MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - physiology Monocytes - drug effects Monocytes - metabolism Oligonucleotide Array Sequence Analysis Real-Time Polymerase Chain Reaction Receptor, PAR-1 - physiology Thrombin - pharmacology Thromboplastin - biosynthesis Thromboplastin - genetics Transcription, Genetic - drug effects Up-Regulation - drug effects Wound Healing - genetics Wound Healing and Inflammation/Infection |
| title | Thrombin selectively induces transcription of genes in human monocytes involved in inflammation and wound healing |
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