THU0012 Observing Dysregulation of Signal Transduction Genes in the WNT Pathway Using two Methods
BackgroundIn recent years, the morphogen pathways (1), and specifically the Wnt pathway has been implicated in the development of fibrosis in Systemic Sclerosis (SSc) (2). Animal studies have shown that dysregulation frizzled related protein (FRZB) (3), frizzled class receptor 4 (FZD4) (4) and secre...
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| Veröffentlicht in: | Annals of the rheumatic diseases 2015-06, Vol.74 (Suppl 2), p.197 |
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| creator | Frost, J.M. Tikly, M. Ramsay, M. Estivill, X. Rabionet, K. |
| description | BackgroundIn recent years, the morphogen pathways (1), and specifically the Wnt pathway has been implicated in the development of fibrosis in Systemic Sclerosis (SSc) (2). Animal studies have shown that dysregulation frizzled related protein (FRZB) (3), frizzled class receptor 4 (FZD4) (4) and secreted frizzled related protein 1 (SFRP1) (5) have been implicated in the pathogenesis of SSc.ObjectivesExamine differential gene expression and methylation status of 84 genes in the Wnt pathway.MethodsSkin biopsies were taken from 8 black South African patients with early ( |
| doi_str_mv | 10.1136/annrheumdis-2015-eular.4452 |
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| fullrecord | <record><control><sourceid>proquest_bmj_p</sourceid><recordid>TN_cdi_proquest_journals_1901771309</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4322500311</sourcerecordid><originalsourceid>FETCH-LOGICAL-b759-59b8caa561a9d49fa0511c11cc7f6bcf8f9165af4d16923f9889da0969fcae733</originalsourceid><addsrcrecordid>eNpNkE1Lw0AQhhdRsFb_w0LPqTv52GSPUrUVqhVM8bhMkt0mpd3U3cTSmxf_qL_EpPUgDAzz8vIwPISMgI0BAn6LxthStduicp7PIPJUu0E7DsPIPyMDCHnSxZydkwFjLPBCweNLcuXcujtZAsmA5OlsyRj4P1_fi8wp-1mZFb0_OKtWHaqpakNrTd-qlcENTS0aV7T5MZ4qoxytDG1KRd9fUvqKTbnHA126ntHsa_qsmrIu3DW50Lhx6uZvD0n6-JBOZt58MX2a3M29LI6EF4ksyREjDiiKUGhkEUDeTR5rnuU60QJ4hDosgAs_0CJJRIFMcKFzVHEQDMnohN3Z-qNVrpHrurXd306CYBDHEDDRtfiplW3XcmerLdqDBCZ7n_KfT9n7lEefsvcZ_AK_v2-c</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1901771309</pqid></control><display><type>article</type><title>THU0012 Observing Dysregulation of Signal Transduction Genes in the WNT Pathway Using two Methods</title><source>BMJ Journals - NESLi2</source><creator>Frost, J.M. ; Tikly, M. ; Ramsay, M. ; Estivill, X. ; Rabionet, K.</creator><creatorcontrib>Frost, J.M. ; Tikly, M. ; Ramsay, M. ; Estivill, X. ; Rabionet, K.</creatorcontrib><description>BackgroundIn recent years, the morphogen pathways (1), and specifically the Wnt pathway has been implicated in the development of fibrosis in Systemic Sclerosis (SSc) (2). Animal studies have shown that dysregulation frizzled related protein (FRZB) (3), frizzled class receptor 4 (FZD4) (4) and secreted frizzled related protein 1 (SFRP1) (5) have been implicated in the pathogenesis of SSc.ObjectivesExamine differential gene expression and methylation status of 84 genes in the Wnt pathway.MethodsSkin biopsies were taken from 8 black South African patients with early (<6 years) diffuse SSc, one from the lateral forearm (involved) and one from the back (uninvolved). Data was generated using the Wnt pathway RT2 Profiler and Epitect Methyl qPCR Arrays, as well as mRNA-sequencing. Data was analysed using HTqPCR and DESeq2.ResultsThe expression data from the qPCR array suggests that the 8 patients are segregating into two groups, and that the most significantly expressed genes are involved in signal transduction within the Wnt pathway. Results can be seen in the table below. There was no significant difference in gene expression between Involved and Uninvolved skin samples. Analysis of the methylation status of 22 Wnt pathway genes revealed no significant results.Table 1.qPCRmRNA-seqCvInvp-valueCvUninvp-valueCvInvp-valueCvUninvp-valueFRZB16.190.00519.260.0032.010.0011.30.074FZD42.630.0062.700.0092.110.0021.90.007SFRP12.710.0513.350.0181.90.0071.680.021ConclusionsThe results of this study suggest that the dysregulation of Wnt pathway signal transduction is involved in the development of fibrosis in SSc in humans. Interestingly, although patients are phenotypically similar, they are clustering into two distinct groups based on the differential expression of the Wnt pathway genes. Involved and Uninvolved skin exhibit similar magnitudes of expression. Identification of dysregulated genes in the pathway may provide novel insights into the pathogenesis of SSc and hence potential new targets for therapy.ReferencesDistler et al. (2014) Ann Rheum Dis. 73(6): 1265-8Lafyatis (2012) Nat Rev Rheumatol. 8(8): 441-2De Langhe et al. (2014) Fibrogenesis Tissue Repair. 7(14)Igota et al. (2013) Int J Med Sci. 10(4): 344-54Dees et al. (2014) Ann Rheum Dis. 73(6): 1232-9Acknowledgements1. Wits-Novartis-CRG Scientist Exchange Program. 2. National Research Foundation South Africa. 3. Estivill Lab (CRG, Barcelona, Spain). 4. Frank Staedtler (Novartis, Basel, Switzerland.Disclosure of InterestNone declared</description><identifier>ISSN: 0003-4967</identifier><identifier>EISSN: 1468-2060</identifier><identifier>DOI: 10.1136/annrheumdis-2015-eular.4452</identifier><identifier>CODEN: ARDIAO</identifier><language>eng</language><publisher>London: BMJ Publishing Group LTD</publisher><ispartof>Annals of the rheumatic diseases, 2015-06, Vol.74 (Suppl 2), p.197</ispartof><rights>2015, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>Copyright: 2015 (c) 2015, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://ard.bmj.com/content/74/Suppl_2/197.1.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://ard.bmj.com/content/74/Suppl_2/197.1.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,780,784,23571,27924,27925,77600,77631</link.rule.ids></links><search><creatorcontrib>Frost, J.M.</creatorcontrib><creatorcontrib>Tikly, M.</creatorcontrib><creatorcontrib>Ramsay, M.</creatorcontrib><creatorcontrib>Estivill, X.</creatorcontrib><creatorcontrib>Rabionet, K.</creatorcontrib><title>THU0012 Observing Dysregulation of Signal Transduction Genes in the WNT Pathway Using two Methods</title><title>Annals of the rheumatic diseases</title><description>BackgroundIn recent years, the morphogen pathways (1), and specifically the Wnt pathway has been implicated in the development of fibrosis in Systemic Sclerosis (SSc) (2). Animal studies have shown that dysregulation frizzled related protein (FRZB) (3), frizzled class receptor 4 (FZD4) (4) and secreted frizzled related protein 1 (SFRP1) (5) have been implicated in the pathogenesis of SSc.ObjectivesExamine differential gene expression and methylation status of 84 genes in the Wnt pathway.MethodsSkin biopsies were taken from 8 black South African patients with early (<6 years) diffuse SSc, one from the lateral forearm (involved) and one from the back (uninvolved). Data was generated using the Wnt pathway RT2 Profiler and Epitect Methyl qPCR Arrays, as well as mRNA-sequencing. Data was analysed using HTqPCR and DESeq2.ResultsThe expression data from the qPCR array suggests that the 8 patients are segregating into two groups, and that the most significantly expressed genes are involved in signal transduction within the Wnt pathway. Results can be seen in the table below. There was no significant difference in gene expression between Involved and Uninvolved skin samples. Analysis of the methylation status of 22 Wnt pathway genes revealed no significant results.Table 1.qPCRmRNA-seqCvInvp-valueCvUninvp-valueCvInvp-valueCvUninvp-valueFRZB16.190.00519.260.0032.010.0011.30.074FZD42.630.0062.700.0092.110.0021.90.007SFRP12.710.0513.350.0181.90.0071.680.021ConclusionsThe results of this study suggest that the dysregulation of Wnt pathway signal transduction is involved in the development of fibrosis in SSc in humans. Interestingly, although patients are phenotypically similar, they are clustering into two distinct groups based on the differential expression of the Wnt pathway genes. Involved and Uninvolved skin exhibit similar magnitudes of expression. Identification of dysregulated genes in the pathway may provide novel insights into the pathogenesis of SSc and hence potential new targets for therapy.ReferencesDistler et al. (2014) Ann Rheum Dis. 73(6): 1265-8Lafyatis (2012) Nat Rev Rheumatol. 8(8): 441-2De Langhe et al. (2014) Fibrogenesis Tissue Repair. 7(14)Igota et al. (2013) Int J Med Sci. 10(4): 344-54Dees et al. (2014) Ann Rheum Dis. 73(6): 1232-9Acknowledgements1. Wits-Novartis-CRG Scientist Exchange Program. 2. National Research Foundation South Africa. 3. Estivill Lab (CRG, Barcelona, Spain). 4. Frank Staedtler (Novartis, Basel, Switzerland.Disclosure of InterestNone declared</description><issn>0003-4967</issn><issn>1468-2060</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpNkE1Lw0AQhhdRsFb_w0LPqTv52GSPUrUVqhVM8bhMkt0mpd3U3cTSmxf_qL_EpPUgDAzz8vIwPISMgI0BAn6LxthStduicp7PIPJUu0E7DsPIPyMDCHnSxZydkwFjLPBCweNLcuXcujtZAsmA5OlsyRj4P1_fi8wp-1mZFb0_OKtWHaqpakNrTd-qlcENTS0aV7T5MZ4qoxytDG1KRd9fUvqKTbnHA126ntHsa_qsmrIu3DW50Lhx6uZvD0n6-JBOZt58MX2a3M29LI6EF4ksyREjDiiKUGhkEUDeTR5rnuU60QJ4hDosgAs_0CJJRIFMcKFzVHEQDMnohN3Z-qNVrpHrurXd306CYBDHEDDRtfiplW3XcmerLdqDBCZ7n_KfT9n7lEefsvcZ_AK_v2-c</recordid><startdate>201506</startdate><enddate>201506</enddate><creator>Frost, J.M.</creator><creator>Tikly, M.</creator><creator>Ramsay, M.</creator><creator>Estivill, X.</creator><creator>Rabionet, K.</creator><general>BMJ Publishing Group LTD</general><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope></search><sort><creationdate>201506</creationdate><title>THU0012 Observing Dysregulation of Signal Transduction Genes in the WNT Pathway Using two Methods</title><author>Frost, J.M. ; Tikly, M. ; Ramsay, M. ; Estivill, X. ; Rabionet, K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b759-59b8caa561a9d49fa0511c11cc7f6bcf8f9165af4d16923f9889da0969fcae733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Frost, J.M.</creatorcontrib><creatorcontrib>Tikly, M.</creatorcontrib><creatorcontrib>Ramsay, M.</creatorcontrib><creatorcontrib>Estivill, X.</creatorcontrib><creatorcontrib>Rabionet, K.</creatorcontrib><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM 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>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</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>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</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 Central Basic</collection><jtitle>Annals of the rheumatic diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Frost, J.M.</au><au>Tikly, M.</au><au>Ramsay, M.</au><au>Estivill, X.</au><au>Rabionet, K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>THU0012 Observing Dysregulation of Signal Transduction Genes in the WNT Pathway Using two Methods</atitle><jtitle>Annals of the rheumatic diseases</jtitle><date>2015-06</date><risdate>2015</risdate><volume>74</volume><issue>Suppl 2</issue><spage>197</spage><pages>197-</pages><issn>0003-4967</issn><eissn>1468-2060</eissn><coden>ARDIAO</coden><abstract>BackgroundIn recent years, the morphogen pathways (1), and specifically the Wnt pathway has been implicated in the development of fibrosis in Systemic Sclerosis (SSc) (2). Animal studies have shown that dysregulation frizzled related protein (FRZB) (3), frizzled class receptor 4 (FZD4) (4) and secreted frizzled related protein 1 (SFRP1) (5) have been implicated in the pathogenesis of SSc.ObjectivesExamine differential gene expression and methylation status of 84 genes in the Wnt pathway.MethodsSkin biopsies were taken from 8 black South African patients with early (<6 years) diffuse SSc, one from the lateral forearm (involved) and one from the back (uninvolved). Data was generated using the Wnt pathway RT2 Profiler and Epitect Methyl qPCR Arrays, as well as mRNA-sequencing. Data was analysed using HTqPCR and DESeq2.ResultsThe expression data from the qPCR array suggests that the 8 patients are segregating into two groups, and that the most significantly expressed genes are involved in signal transduction within the Wnt pathway. Results can be seen in the table below. There was no significant difference in gene expression between Involved and Uninvolved skin samples. Analysis of the methylation status of 22 Wnt pathway genes revealed no significant results.Table 1.qPCRmRNA-seqCvInvp-valueCvUninvp-valueCvInvp-valueCvUninvp-valueFRZB16.190.00519.260.0032.010.0011.30.074FZD42.630.0062.700.0092.110.0021.90.007SFRP12.710.0513.350.0181.90.0071.680.021ConclusionsThe results of this study suggest that the dysregulation of Wnt pathway signal transduction is involved in the development of fibrosis in SSc in humans. Interestingly, although patients are phenotypically similar, they are clustering into two distinct groups based on the differential expression of the Wnt pathway genes. Involved and Uninvolved skin exhibit similar magnitudes of expression. Identification of dysregulated genes in the pathway may provide novel insights into the pathogenesis of SSc and hence potential new targets for therapy.ReferencesDistler et al. (2014) Ann Rheum Dis. 73(6): 1265-8Lafyatis (2012) Nat Rev Rheumatol. 8(8): 441-2De Langhe et al. (2014) Fibrogenesis Tissue Repair. 7(14)Igota et al. (2013) Int J Med Sci. 10(4): 344-54Dees et al. (2014) Ann Rheum Dis. 73(6): 1232-9Acknowledgements1. Wits-Novartis-CRG Scientist Exchange Program. 2. National Research Foundation South Africa. 3. Estivill Lab (CRG, Barcelona, Spain). 4. Frank Staedtler (Novartis, Basel, Switzerland.Disclosure of InterestNone declared</abstract><cop>London</cop><pub>BMJ Publishing Group LTD</pub><doi>10.1136/annrheumdis-2015-eular.4452</doi></addata></record> |
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| title | THU0012 Observing Dysregulation of Signal Transduction Genes in the WNT Pathway Using two Methods |
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