CTGF/CCN2 activates canonical Wnt signalling in mesangial cells through LRP6: Implications for the pathogenesis of diabetic nephropathy
We describe the activation of Wnt signalling in mesangial cells by CCN2. CCN2 stimulates phosphorylation of LRP6 and GSK-3β resulting in accumulation and nuclear localisation of β-catenin, TCF/LEF activity and expression of Wnt targets. This is coincident with decreased phosphorylation of β-catenin...
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| Veröffentlicht in: | FEBS letters 2011-02, Vol.585 (3), p.531-538 |
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| creator | Rooney, Brian O’Donovan, Helen Gaffney, Andrew Browne, Marie Faherty, Noel Curran, Simon P. Sadlier, Denise Godson, Catherine Brazil, Derek P. Crean, John |
| description | We describe the activation of Wnt signalling in mesangial cells by CCN2. CCN2 stimulates phosphorylation of LRP6 and GSK-3β resulting in accumulation and nuclear localisation of β-catenin, TCF/LEF activity and expression of Wnt targets. This is coincident with decreased phosphorylation of β-catenin on Ser 33/37 and increased phosphorylation on Tyr142. DKK-1 and LRP6 siRNA reversed CCN2’s effects. Microarray analyses of diabetic patients identified differentially expressed Wnt components. β-Catenin is increased in type 1 diabetic and UUO mice and in
in vitro models of hyperglycaemia and hypertension. These findings suggest that Wnt/CCN2 signalling plays a role in the pathogenesis of diabetic nephropathy. |
| doi_str_mv | 10.1016/j.febslet.2011.01.004 |
| format | Article |
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in vitro models of hyperglycaemia and hypertension. These findings suggest that Wnt/CCN2 signalling plays a role in the pathogenesis of diabetic nephropathy.</description><identifier>ISSN: 0014-5793</identifier><identifier>EISSN: 1873-3468</identifier><identifier>DOI: 10.1016/j.febslet.2011.01.004</identifier><identifier>PMID: 21237163</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>Animals ; beta Catenin - metabolism ; Cells, Cultured ; Connective tissue growth factor ; Connective Tissue Growth Factor - genetics ; Connective Tissue Growth Factor - metabolism ; Diabetes Mellitus, Type 1 - chemically induced ; Diabetes Mellitus, Type 1 - metabolism ; Diabetes Mellitus, Type 1 - pathology ; Diabetic Nephropathies - metabolism ; Diabetic Nephropathies - pathology ; Diabetic Nephropathies - physiopathology ; Diabetic nephropathy ; gene expression regulation ; Glycogen Synthase Kinase 3 - metabolism ; Glycogen Synthase Kinase 3 beta ; Glycogen synthase kinase 3β ; Humans ; hyperglycemia ; Hyperglycemia - metabolism ; hypertension ; Hypertension - metabolism ; in vitro studies ; Kidney Cortex - metabolism ; Kidney Cortex - pathology ; LDL-Receptor Related Proteins - genetics ; LDL-Receptor Related Proteins - metabolism ; Low Density Lipoprotein Receptor-Related Protein-6 ; LRP6 ; Male ; Mesangial Cells - cytology ; Mesangial Cells - metabolism ; Mice ; Mice, Inbred C57BL ; microarray technology ; pathogenesis ; patients ; Phosphorylation ; Protein Transport ; RNA, Small Interfering ; Signal Transduction ; small interfering RNA ; Ureteral Obstruction - metabolism ; Ureteral Obstruction - pathology ; Wnt ; Wnt Proteins - metabolism ; β-Catenin</subject><ispartof>FEBS letters, 2011-02, Vol.585 (3), p.531-538</ispartof><rights>2011 Federation of European Biochemical Societies</rights><rights>FEBS Letters 585 (2011) 1873-3468 © 2015 Federation of European Biochemical Societies</rights><rights>Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500X-c3b9c9f0b3ea45d33bee84bed0fabb0228423248bf017a73c167b4f3653bf60d3</citedby><cites>FETCH-LOGICAL-c500X-c3b9c9f0b3ea45d33bee84bed0fabb0228423248bf017a73c167b4f3653bf60d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1016%2Fj.febslet.2011.01.004$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S001457931100024X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,1427,3537,27903,27904,45553,45554,46387,46811,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21237163$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rooney, Brian</creatorcontrib><creatorcontrib>O’Donovan, Helen</creatorcontrib><creatorcontrib>Gaffney, Andrew</creatorcontrib><creatorcontrib>Browne, Marie</creatorcontrib><creatorcontrib>Faherty, Noel</creatorcontrib><creatorcontrib>Curran, Simon P.</creatorcontrib><creatorcontrib>Sadlier, Denise</creatorcontrib><creatorcontrib>Godson, Catherine</creatorcontrib><creatorcontrib>Brazil, Derek P.</creatorcontrib><creatorcontrib>Crean, John</creatorcontrib><title>CTGF/CCN2 activates canonical Wnt signalling in mesangial cells through LRP6: Implications for the pathogenesis of diabetic nephropathy</title><title>FEBS letters</title><addtitle>FEBS Lett</addtitle><description>We describe the activation of Wnt signalling in mesangial cells by CCN2. CCN2 stimulates phosphorylation of LRP6 and GSK-3β resulting in accumulation and nuclear localisation of β-catenin, TCF/LEF activity and expression of Wnt targets. This is coincident with decreased phosphorylation of β-catenin on Ser 33/37 and increased phosphorylation on Tyr142. DKK-1 and LRP6 siRNA reversed CCN2’s effects. Microarray analyses of diabetic patients identified differentially expressed Wnt components. β-Catenin is increased in type 1 diabetic and UUO mice and in
in vitro models of hyperglycaemia and hypertension. These findings suggest that Wnt/CCN2 signalling plays a role in the pathogenesis of diabetic nephropathy.</description><subject>Animals</subject><subject>beta Catenin - metabolism</subject><subject>Cells, Cultured</subject><subject>Connective tissue growth factor</subject><subject>Connective Tissue Growth Factor - genetics</subject><subject>Connective Tissue Growth Factor - metabolism</subject><subject>Diabetes Mellitus, Type 1 - chemically induced</subject><subject>Diabetes Mellitus, Type 1 - metabolism</subject><subject>Diabetes Mellitus, Type 1 - pathology</subject><subject>Diabetic Nephropathies - metabolism</subject><subject>Diabetic Nephropathies - pathology</subject><subject>Diabetic Nephropathies - physiopathology</subject><subject>Diabetic nephropathy</subject><subject>gene expression regulation</subject><subject>Glycogen Synthase Kinase 3 - metabolism</subject><subject>Glycogen Synthase Kinase 3 beta</subject><subject>Glycogen synthase kinase 3β</subject><subject>Humans</subject><subject>hyperglycemia</subject><subject>Hyperglycemia - metabolism</subject><subject>hypertension</subject><subject>Hypertension - metabolism</subject><subject>in vitro studies</subject><subject>Kidney Cortex - metabolism</subject><subject>Kidney Cortex - pathology</subject><subject>LDL-Receptor Related Proteins - genetics</subject><subject>LDL-Receptor Related Proteins - metabolism</subject><subject>Low Density Lipoprotein Receptor-Related Protein-6</subject><subject>LRP6</subject><subject>Male</subject><subject>Mesangial Cells - cytology</subject><subject>Mesangial Cells - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>microarray technology</subject><subject>pathogenesis</subject><subject>patients</subject><subject>Phosphorylation</subject><subject>Protein Transport</subject><subject>RNA, Small Interfering</subject><subject>Signal Transduction</subject><subject>small interfering RNA</subject><subject>Ureteral Obstruction - metabolism</subject><subject>Ureteral Obstruction - pathology</subject><subject>Wnt</subject><subject>Wnt Proteins - metabolism</subject><subject>β-Catenin</subject><issn>0014-5793</issn><issn>1873-3468</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUctu1DAUjRCIDoVPALxjlalfeQwbVKJOW2kEiLaiO8t2rjMeJXaIM63mC_rbOGRgC9KVLOs8rs49SfKW4CXBJD_bLQ2o0MK4pJiQJY6D-bNkQcqCpYzn5fNkgTHhaVas2EnyKoQdjv-SrF4mJ5RQVpCcLZKn6vZyfVZVXyiSerQPcoSAtHTeWS1b9MONKNjGyba1rkHWoQ6CdI2NmIa2DWjcDn7fbNHm-7f8I7ru-jYKR-tdQMYPEQbUy3HrG3AQbEDeoNpKBaPVyEEf1RN8eJ28MLIN8Ob4niZ364vb6irdfL28rs43qc4wvk81Uyu9MlgxkDyrGVMAJVdQYyOVwpSWnDLKS2UwKWTBNMkLxQ3LM6ZMjmt2mnyYffvB_9xDGEVnw5REOvD7IEpe5mXBWRaZ2czUgw9hACP6wXZyOAiCxVSB2IljBWKqQOA4mEfdu-OGveqg_qv6c_NIuJoJj7aFw_-5ivXFZ3oz9TnVSUiskvL7aPV-tjLSC9kMNoi7myiLtyK4KH6n-DQzIB71wcIggrbgNNR2AD2K2tt_5PkFec-6eQ</recordid><startdate>20110204</startdate><enddate>20110204</enddate><creator>Rooney, Brian</creator><creator>O’Donovan, Helen</creator><creator>Gaffney, Andrew</creator><creator>Browne, Marie</creator><creator>Faherty, Noel</creator><creator>Curran, Simon P.</creator><creator>Sadlier, Denise</creator><creator>Godson, Catherine</creator><creator>Brazil, Derek P.</creator><creator>Crean, John</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</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>20110204</creationdate><title>CTGF/CCN2 activates canonical Wnt signalling in mesangial cells through LRP6: Implications for the pathogenesis of diabetic nephropathy</title><author>Rooney, Brian ; O’Donovan, Helen ; Gaffney, Andrew ; Browne, Marie ; Faherty, Noel ; Curran, Simon P. ; Sadlier, Denise ; Godson, Catherine ; Brazil, Derek P. ; Crean, John</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c500X-c3b9c9f0b3ea45d33bee84bed0fabb0228423248bf017a73c167b4f3653bf60d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>beta Catenin - metabolism</topic><topic>Cells, Cultured</topic><topic>Connective tissue growth factor</topic><topic>Connective Tissue Growth Factor - genetics</topic><topic>Connective Tissue Growth Factor - metabolism</topic><topic>Diabetes Mellitus, Type 1 - chemically induced</topic><topic>Diabetes Mellitus, Type 1 - metabolism</topic><topic>Diabetes Mellitus, Type 1 - pathology</topic><topic>Diabetic Nephropathies - metabolism</topic><topic>Diabetic Nephropathies - pathology</topic><topic>Diabetic Nephropathies - physiopathology</topic><topic>Diabetic nephropathy</topic><topic>gene expression regulation</topic><topic>Glycogen Synthase Kinase 3 - metabolism</topic><topic>Glycogen Synthase Kinase 3 beta</topic><topic>Glycogen synthase kinase 3β</topic><topic>Humans</topic><topic>hyperglycemia</topic><topic>Hyperglycemia - metabolism</topic><topic>hypertension</topic><topic>Hypertension - metabolism</topic><topic>in vitro studies</topic><topic>Kidney Cortex - metabolism</topic><topic>Kidney Cortex - pathology</topic><topic>LDL-Receptor Related Proteins - genetics</topic><topic>LDL-Receptor Related Proteins - metabolism</topic><topic>Low Density Lipoprotein Receptor-Related Protein-6</topic><topic>LRP6</topic><topic>Male</topic><topic>Mesangial Cells - cytology</topic><topic>Mesangial Cells - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>microarray technology</topic><topic>pathogenesis</topic><topic>patients</topic><topic>Phosphorylation</topic><topic>Protein Transport</topic><topic>RNA, Small Interfering</topic><topic>Signal Transduction</topic><topic>small interfering RNA</topic><topic>Ureteral Obstruction - metabolism</topic><topic>Ureteral Obstruction - pathology</topic><topic>Wnt</topic><topic>Wnt Proteins - metabolism</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rooney, Brian</creatorcontrib><creatorcontrib>O’Donovan, Helen</creatorcontrib><creatorcontrib>Gaffney, Andrew</creatorcontrib><creatorcontrib>Browne, Marie</creatorcontrib><creatorcontrib>Faherty, Noel</creatorcontrib><creatorcontrib>Curran, Simon P.</creatorcontrib><creatorcontrib>Sadlier, Denise</creatorcontrib><creatorcontrib>Godson, Catherine</creatorcontrib><creatorcontrib>Brazil, Derek P.</creatorcontrib><creatorcontrib>Crean, John</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</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>FEBS letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rooney, Brian</au><au>O’Donovan, Helen</au><au>Gaffney, Andrew</au><au>Browne, Marie</au><au>Faherty, Noel</au><au>Curran, Simon P.</au><au>Sadlier, Denise</au><au>Godson, Catherine</au><au>Brazil, Derek P.</au><au>Crean, John</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CTGF/CCN2 activates canonical Wnt signalling in mesangial cells through LRP6: Implications for the pathogenesis of diabetic nephropathy</atitle><jtitle>FEBS letters</jtitle><addtitle>FEBS Lett</addtitle><date>2011-02-04</date><risdate>2011</risdate><volume>585</volume><issue>3</issue><spage>531</spage><epage>538</epage><pages>531-538</pages><issn>0014-5793</issn><eissn>1873-3468</eissn><abstract>We describe the activation of Wnt signalling in mesangial cells by CCN2. CCN2 stimulates phosphorylation of LRP6 and GSK-3β resulting in accumulation and nuclear localisation of β-catenin, TCF/LEF activity and expression of Wnt targets. This is coincident with decreased phosphorylation of β-catenin on Ser 33/37 and increased phosphorylation on Tyr142. DKK-1 and LRP6 siRNA reversed CCN2’s effects. Microarray analyses of diabetic patients identified differentially expressed Wnt components. β-Catenin is increased in type 1 diabetic and UUO mice and in
in vitro models of hyperglycaemia and hypertension. These findings suggest that Wnt/CCN2 signalling plays a role in the pathogenesis of diabetic nephropathy.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>21237163</pmid><doi>10.1016/j.febslet.2011.01.004</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals beta Catenin - metabolism Cells, Cultured Connective tissue growth factor Connective Tissue Growth Factor - genetics Connective Tissue Growth Factor - metabolism Diabetes Mellitus, Type 1 - chemically induced Diabetes Mellitus, Type 1 - metabolism Diabetes Mellitus, Type 1 - pathology Diabetic Nephropathies - metabolism Diabetic Nephropathies - pathology Diabetic Nephropathies - physiopathology Diabetic nephropathy gene expression regulation Glycogen Synthase Kinase 3 - metabolism Glycogen Synthase Kinase 3 beta Glycogen synthase kinase 3β Humans hyperglycemia Hyperglycemia - metabolism hypertension Hypertension - metabolism in vitro studies Kidney Cortex - metabolism Kidney Cortex - pathology LDL-Receptor Related Proteins - genetics LDL-Receptor Related Proteins - metabolism Low Density Lipoprotein Receptor-Related Protein-6 LRP6 Male Mesangial Cells - cytology Mesangial Cells - metabolism Mice Mice, Inbred C57BL microarray technology pathogenesis patients Phosphorylation Protein Transport RNA, Small Interfering Signal Transduction small interfering RNA Ureteral Obstruction - metabolism Ureteral Obstruction - pathology Wnt Wnt Proteins - metabolism β-Catenin |
| title | CTGF/CCN2 activates canonical Wnt signalling in mesangial cells through LRP6: Implications for the pathogenesis of diabetic nephropathy |
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