Large-scale profiling of signalling pathways reveals an asthma specific signature in bronchial smooth muscle cells
Bronchial smooth muscle (BSM) cells from asthmatic patients maintain in vitro a distinct hyper-reactive ("primed") phenotype, characterized by increased release of pro-inflammatory factors and mediators, as well as hyperplasia and/or hypertrophy. This "primed" phenotype helps to...
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| creator | Alexandrova, Elena Nassa, Giovanni Corleone, Giacomo Buzdin, Anton Aliper, Alexander M Terekhanova, Nadezhda Shepelin, Denis Zhavoronkov, Alexander Tamm, Michael Milanesi, Luciano Miglino, Nicola Weisz, Alessandro Borger, Pieter |
| description | Bronchial smooth muscle (BSM) cells from asthmatic patients maintain in vitro a distinct hyper-reactive ("primed") phenotype, characterized by increased release of pro-inflammatory factors and mediators, as well as hyperplasia and/or hypertrophy. This "primed" phenotype helps to understand pathogenesis of asthma, as changes in BSM function are essential for manifestation of allergic and inflammatory responses and airway wall remodelling.
To identify signalling pathways in cultured primary BSMs of asthma patients and non-asthmatic subjects by genome wide profiling of differentially expressed mRNAs and activated intracellular signalling pathways (ISPs).
Transcriptome profiling by cap-analysis-of-gene-expression (CAGE), which permits selection of preferentially capped mRNAs most likely to be translated into proteins, was performed in human BSM cells from asthmatic (n=8) and non-asthmatic (n=6) subjects and OncoFinder tool were then exploited for identification of ISP deregulations.
CAGE revealed >600 RNAs differentially expressed in asthma vs control cells (p≤0.005), with asthma samples showing a high degree of similarity among them. Comprehensive ISP activation analysis revealed that among 269 pathways analysed, 145 (p |
| doi_str_mv | 10.18632/oncotarget.7209 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5039037</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1812891436</sourcerecordid><originalsourceid>FETCH-LOGICAL-c354t-8ba5083404206f99353059dcdc6c048249d5e33a419a281b6ee9eab5d64751e23</originalsourceid><addsrcrecordid>eNpVkU1P3DAQhq2KikXbvXNCPvaSrT-z8QUJIQqVVuqlPVsTZ7JxlcTBdqj4982ylNK5eEaeed6xX0IuOdvyqpTiSxhdyBAPmLc7wcwHcsGNMoXQWp69y1dkk9IvtoRWu0qYc7IS5QIopbogcX8EFMlBj3SKofW9Hw80tDT5wwj9SzVB7n7Dc6IRnxD6RGGkkHI3AE0TOt96d2rPc0TqR1rHZbfOQ0_TEELu6DAntwg47Pv0iXxsFwhuXs81-fn17sftQ7H_fv_t9mZfOKlVLqoaNKukYkqwsjVGasm0aVzjSsdUJZRpNEoJihsQFa9LRINQ66ZUO81RyDW5PnGnuR6wcTjmCL2doh8gPtsA3v5_M_rOHsKT1UwaJncL4PMrIIbHGVO2g0_HJ8CIYU6WV1xUhqvlJ9eEnVpdDClFbN9kOLMvbtl_btmjW8vI1fv13gb-eiP_AP-KliA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1812891436</pqid></control><display><type>article</type><title>Large-scale profiling of signalling pathways reveals an asthma specific signature in bronchial smooth muscle cells</title><source>MEDLINE</source><source>PubMed Central Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free E- Journals</source><creator>Alexandrova, Elena ; Nassa, Giovanni ; Corleone, Giacomo ; Buzdin, Anton ; Aliper, Alexander M ; Terekhanova, Nadezhda ; Shepelin, Denis ; Zhavoronkov, Alexander ; Tamm, Michael ; Milanesi, Luciano ; Miglino, Nicola ; Weisz, Alessandro ; Borger, Pieter</creator><creatorcontrib>Alexandrova, Elena ; Nassa, Giovanni ; Corleone, Giacomo ; Buzdin, Anton ; Aliper, Alexander M ; Terekhanova, Nadezhda ; Shepelin, Denis ; Zhavoronkov, Alexander ; Tamm, Michael ; Milanesi, Luciano ; Miglino, Nicola ; Weisz, Alessandro ; Borger, Pieter</creatorcontrib><description>Bronchial smooth muscle (BSM) cells from asthmatic patients maintain in vitro a distinct hyper-reactive ("primed") phenotype, characterized by increased release of pro-inflammatory factors and mediators, as well as hyperplasia and/or hypertrophy. This "primed" phenotype helps to understand pathogenesis of asthma, as changes in BSM function are essential for manifestation of allergic and inflammatory responses and airway wall remodelling.
To identify signalling pathways in cultured primary BSMs of asthma patients and non-asthmatic subjects by genome wide profiling of differentially expressed mRNAs and activated intracellular signalling pathways (ISPs).
Transcriptome profiling by cap-analysis-of-gene-expression (CAGE), which permits selection of preferentially capped mRNAs most likely to be translated into proteins, was performed in human BSM cells from asthmatic (n=8) and non-asthmatic (n=6) subjects and OncoFinder tool were then exploited for identification of ISP deregulations.
CAGE revealed >600 RNAs differentially expressed in asthma vs control cells (p≤0.005), with asthma samples showing a high degree of similarity among them. Comprehensive ISP activation analysis revealed that among 269 pathways analysed, 145 (p<0.05) or 103 (p<0.01) are differentially active in asthma, with profiles that clearly characterize BSM cells of asthmatic individuals. Notably, we identified 7 clusters of coherently acting pathways functionally related to the disease, with ISPs down-regulated in asthma mostly targeting cell death-promoting pathways and up-regulated ones affecting cell growth and proliferation, inflammatory response, control of smooth muscle contraction and hypoxia-related signalization.
These first-time results can now be exploited toward development of novel therapeutic strategies targeting ISP signatures linked to asthma pathophysiology.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.7209</identifier><identifier>PMID: 26863634</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Adult ; Aged ; Asthma - metabolism ; Bronchi - metabolism ; Female ; Gene Expression Profiling - methods ; Humans ; Male ; Middle Aged ; Myocytes, Smooth Muscle - metabolism ; Research Paper ; Signal Transduction - physiology ; Transcriptome ; Young Adult</subject><ispartof>Oncotarget, 2016-05, Vol.7 (18), p.25150-25161</ispartof><rights>Copyright: © 2016 Alexandrova et al. 2016</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c354t-8ba5083404206f99353059dcdc6c048249d5e33a419a281b6ee9eab5d64751e23</citedby><cites>FETCH-LOGICAL-c354t-8ba5083404206f99353059dcdc6c048249d5e33a419a281b6ee9eab5d64751e23</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/PMC5039037/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039037/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27915,27916,53782,53784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26863634$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alexandrova, Elena</creatorcontrib><creatorcontrib>Nassa, Giovanni</creatorcontrib><creatorcontrib>Corleone, Giacomo</creatorcontrib><creatorcontrib>Buzdin, Anton</creatorcontrib><creatorcontrib>Aliper, Alexander M</creatorcontrib><creatorcontrib>Terekhanova, Nadezhda</creatorcontrib><creatorcontrib>Shepelin, Denis</creatorcontrib><creatorcontrib>Zhavoronkov, Alexander</creatorcontrib><creatorcontrib>Tamm, Michael</creatorcontrib><creatorcontrib>Milanesi, Luciano</creatorcontrib><creatorcontrib>Miglino, Nicola</creatorcontrib><creatorcontrib>Weisz, Alessandro</creatorcontrib><creatorcontrib>Borger, Pieter</creatorcontrib><title>Large-scale profiling of signalling pathways reveals an asthma specific signature in bronchial smooth muscle cells</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Bronchial smooth muscle (BSM) cells from asthmatic patients maintain in vitro a distinct hyper-reactive ("primed") phenotype, characterized by increased release of pro-inflammatory factors and mediators, as well as hyperplasia and/or hypertrophy. This "primed" phenotype helps to understand pathogenesis of asthma, as changes in BSM function are essential for manifestation of allergic and inflammatory responses and airway wall remodelling.
To identify signalling pathways in cultured primary BSMs of asthma patients and non-asthmatic subjects by genome wide profiling of differentially expressed mRNAs and activated intracellular signalling pathways (ISPs).
Transcriptome profiling by cap-analysis-of-gene-expression (CAGE), which permits selection of preferentially capped mRNAs most likely to be translated into proteins, was performed in human BSM cells from asthmatic (n=8) and non-asthmatic (n=6) subjects and OncoFinder tool were then exploited for identification of ISP deregulations.
CAGE revealed >600 RNAs differentially expressed in asthma vs control cells (p≤0.005), with asthma samples showing a high degree of similarity among them. Comprehensive ISP activation analysis revealed that among 269 pathways analysed, 145 (p<0.05) or 103 (p<0.01) are differentially active in asthma, with profiles that clearly characterize BSM cells of asthmatic individuals. Notably, we identified 7 clusters of coherently acting pathways functionally related to the disease, with ISPs down-regulated in asthma mostly targeting cell death-promoting pathways and up-regulated ones affecting cell growth and proliferation, inflammatory response, control of smooth muscle contraction and hypoxia-related signalization.
These first-time results can now be exploited toward development of novel therapeutic strategies targeting ISP signatures linked to asthma pathophysiology.</description><subject>Adult</subject><subject>Aged</subject><subject>Asthma - metabolism</subject><subject>Bronchi - metabolism</subject><subject>Female</subject><subject>Gene Expression Profiling - methods</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Research Paper</subject><subject>Signal Transduction - physiology</subject><subject>Transcriptome</subject><subject>Young Adult</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1P3DAQhq2KikXbvXNCPvaSrT-z8QUJIQqVVuqlPVsTZ7JxlcTBdqj4982ylNK5eEaeed6xX0IuOdvyqpTiSxhdyBAPmLc7wcwHcsGNMoXQWp69y1dkk9IvtoRWu0qYc7IS5QIopbogcX8EFMlBj3SKofW9Hw80tDT5wwj9SzVB7n7Dc6IRnxD6RGGkkHI3AE0TOt96d2rPc0TqR1rHZbfOQ0_TEELu6DAntwg47Pv0iXxsFwhuXs81-fn17sftQ7H_fv_t9mZfOKlVLqoaNKukYkqwsjVGasm0aVzjSsdUJZRpNEoJihsQFa9LRINQ66ZUO81RyDW5PnGnuR6wcTjmCL2doh8gPtsA3v5_M_rOHsKT1UwaJncL4PMrIIbHGVO2g0_HJ8CIYU6WV1xUhqvlJ9eEnVpdDClFbN9kOLMvbtl_btmjW8vI1fv13gb-eiP_AP-KliA</recordid><startdate>20160503</startdate><enddate>20160503</enddate><creator>Alexandrova, Elena</creator><creator>Nassa, Giovanni</creator><creator>Corleone, Giacomo</creator><creator>Buzdin, Anton</creator><creator>Aliper, Alexander M</creator><creator>Terekhanova, Nadezhda</creator><creator>Shepelin, Denis</creator><creator>Zhavoronkov, Alexander</creator><creator>Tamm, Michael</creator><creator>Milanesi, Luciano</creator><creator>Miglino, Nicola</creator><creator>Weisz, Alessandro</creator><creator>Borger, Pieter</creator><general>Impact Journals LLC</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160503</creationdate><title>Large-scale profiling of signalling pathways reveals an asthma specific signature in bronchial smooth muscle cells</title><author>Alexandrova, Elena ; Nassa, Giovanni ; Corleone, Giacomo ; Buzdin, Anton ; Aliper, Alexander M ; Terekhanova, Nadezhda ; Shepelin, Denis ; Zhavoronkov, Alexander ; Tamm, Michael ; Milanesi, Luciano ; Miglino, Nicola ; Weisz, Alessandro ; Borger, Pieter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c354t-8ba5083404206f99353059dcdc6c048249d5e33a419a281b6ee9eab5d64751e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Asthma - metabolism</topic><topic>Bronchi - metabolism</topic><topic>Female</topic><topic>Gene Expression Profiling - methods</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>Research Paper</topic><topic>Signal Transduction - physiology</topic><topic>Transcriptome</topic><topic>Young Adult</topic><toplevel>online_resources</toplevel><creatorcontrib>Alexandrova, Elena</creatorcontrib><creatorcontrib>Nassa, Giovanni</creatorcontrib><creatorcontrib>Corleone, Giacomo</creatorcontrib><creatorcontrib>Buzdin, Anton</creatorcontrib><creatorcontrib>Aliper, Alexander M</creatorcontrib><creatorcontrib>Terekhanova, Nadezhda</creatorcontrib><creatorcontrib>Shepelin, Denis</creatorcontrib><creatorcontrib>Zhavoronkov, Alexander</creatorcontrib><creatorcontrib>Tamm, Michael</creatorcontrib><creatorcontrib>Milanesi, Luciano</creatorcontrib><creatorcontrib>Miglino, Nicola</creatorcontrib><creatorcontrib>Weisz, Alessandro</creatorcontrib><creatorcontrib>Borger, Pieter</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alexandrova, Elena</au><au>Nassa, Giovanni</au><au>Corleone, Giacomo</au><au>Buzdin, Anton</au><au>Aliper, Alexander M</au><au>Terekhanova, Nadezhda</au><au>Shepelin, Denis</au><au>Zhavoronkov, Alexander</au><au>Tamm, Michael</au><au>Milanesi, Luciano</au><au>Miglino, Nicola</au><au>Weisz, Alessandro</au><au>Borger, Pieter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Large-scale profiling of signalling pathways reveals an asthma specific signature in bronchial smooth muscle cells</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2016-05-03</date><risdate>2016</risdate><volume>7</volume><issue>18</issue><spage>25150</spage><epage>25161</epage><pages>25150-25161</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Bronchial smooth muscle (BSM) cells from asthmatic patients maintain in vitro a distinct hyper-reactive ("primed") phenotype, characterized by increased release of pro-inflammatory factors and mediators, as well as hyperplasia and/or hypertrophy. This "primed" phenotype helps to understand pathogenesis of asthma, as changes in BSM function are essential for manifestation of allergic and inflammatory responses and airway wall remodelling.
To identify signalling pathways in cultured primary BSMs of asthma patients and non-asthmatic subjects by genome wide profiling of differentially expressed mRNAs and activated intracellular signalling pathways (ISPs).
Transcriptome profiling by cap-analysis-of-gene-expression (CAGE), which permits selection of preferentially capped mRNAs most likely to be translated into proteins, was performed in human BSM cells from asthmatic (n=8) and non-asthmatic (n=6) subjects and OncoFinder tool were then exploited for identification of ISP deregulations.
CAGE revealed >600 RNAs differentially expressed in asthma vs control cells (p≤0.005), with asthma samples showing a high degree of similarity among them. Comprehensive ISP activation analysis revealed that among 269 pathways analysed, 145 (p<0.05) or 103 (p<0.01) are differentially active in asthma, with profiles that clearly characterize BSM cells of asthmatic individuals. Notably, we identified 7 clusters of coherently acting pathways functionally related to the disease, with ISPs down-regulated in asthma mostly targeting cell death-promoting pathways and up-regulated ones affecting cell growth and proliferation, inflammatory response, control of smooth muscle contraction and hypoxia-related signalization.
These first-time results can now be exploited toward development of novel therapeutic strategies targeting ISP signatures linked to asthma pathophysiology.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>26863634</pmid><doi>10.18632/oncotarget.7209</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Asthma - metabolism Bronchi - metabolism Female Gene Expression Profiling - methods Humans Male Middle Aged Myocytes, Smooth Muscle - metabolism Research Paper Signal Transduction - physiology Transcriptome Young Adult |
| title | Large-scale profiling of signalling pathways reveals an asthma specific signature in bronchial smooth muscle cells |
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