Alterations in Wnt pathway activity in mouse serum and kidneys during lupus development
Objective The canonical Wnt/β‐catenin pathway was recently identified as a factor in the pathogenesis of several renal diseases. The aim of this study was to evaluate Wnt signaling activity during disease development in a murine model of lupus nephritis. Methods Wnt activity and Dkk‐1 expression wer...
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| Veröffentlicht in: | Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2011-02, Vol.63 (2), p.513-522 |
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| creator | Tveita, Anders Aune Rekvig, Ole Petter |
| description | Objective
The canonical Wnt/β‐catenin pathway was recently identified as a factor in the pathogenesis of several renal diseases. The aim of this study was to evaluate Wnt signaling activity during disease development in a murine model of lupus nephritis.
Methods
Wnt activity and Dkk‐1 expression were serially assayed in the serum and kidneys of (NZB × NZW)F1 mice during progression of lupus nephritis. The effects of serum obtained from mice with lupus and serum‐equivalent concentrations of Dkk‐1 on mesangial cells were assessed in vitro.
Results
Gene expression analyses revealed increased canonical Wnt pathway activity in kidneys during development of lupus nephritis, paralleled by an increase in renal and serum levels of the Wnt inhibitor Dkk‐1. Sera obtained from proteinuric‐stage (NZB × NZW)F1 mice showed strong Wnt‐inhibitory effects in vitro. Dkk‐1 concentrations comparable to those observed in lupus‐prone mice induced apoptosis in tubular and mesangial cells in vitro, whereas no such effect was seen for the range of concentrations observed in young prediseased mice and control BALB/c mice.
Conclusion
These data demonstrate that renal Wnt signaling activity is increased in lupus and is accompanied by an increase in renal and serum levels of Dkk‐1. The Wnt pathway is involved in the turnover of extracellular matrix constituents and represents a potential mediator of the morphologic changes that occur within the glomerulus during the development of nephritis. Furthermore, increased levels of Dkk‐1 serve as a potential proapoptotic stimulus in vitro and possibly in vivo and could be an important element in the initiation and progression of systemic and end‐organ disease manifestations in systemic lupus erythematosus. |
| doi_str_mv | 10.1002/art.30116 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_848687392</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3277852671</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4176-b1337fc7b47dd14075b5c2a84d8f39ab2587e1f57e9df9e99426f915284c50b43</originalsourceid><addsrcrecordid>eNp10EtrFTEUB_Agir1WF34BCYiIi2nznCTLS_EFBUEqXYZM5oymzmTGJNMy397Ue1UQXIUTfpzHH6HnlJxRQti5S-WME0rbB2hHJTMNoZw-RDtCiGi4NPQEPcn5ppaMS_4YnTDKdK3aHbrejwWSK2GOGYeIr2PBiyvf7tyGnS_hNpTt_n-a1ww4Q1on7GKPv4c-wpZxv6YQv-JxXdZawC2M8zJBLE_Ro8GNGZ4d31P05d3bq4sPzeWn9x8v9peNF1S1TUc5V4NXnVB9TwVRspOeOS16PXDjOia1AjpIBaYfDBgjWDuYeqMWXpJO8FP0-tB3SfOPFXKxU8gextFFqCtbLXSrFTesypf_yJt5TbEuZ6mkinDOmKnqzUH5NOecYLBLCpNLm6XE3odta9j2V9jVvjh2XLsJ-j_yd7oVvDoCl70bh-SiD_mv44ZoznR15wd3F0bY_j_R7j9fHUb_BE_glOo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1517033229</pqid></control><display><type>article</type><title>Alterations in Wnt pathway activity in mouse serum and kidneys during lupus development</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Tveita, Anders Aune ; Rekvig, Ole Petter</creator><creatorcontrib>Tveita, Anders Aune ; Rekvig, Ole Petter</creatorcontrib><description>Objective
The canonical Wnt/β‐catenin pathway was recently identified as a factor in the pathogenesis of several renal diseases. The aim of this study was to evaluate Wnt signaling activity during disease development in a murine model of lupus nephritis.
Methods
Wnt activity and Dkk‐1 expression were serially assayed in the serum and kidneys of (NZB × NZW)F1 mice during progression of lupus nephritis. The effects of serum obtained from mice with lupus and serum‐equivalent concentrations of Dkk‐1 on mesangial cells were assessed in vitro.
Results
Gene expression analyses revealed increased canonical Wnt pathway activity in kidneys during development of lupus nephritis, paralleled by an increase in renal and serum levels of the Wnt inhibitor Dkk‐1. Sera obtained from proteinuric‐stage (NZB × NZW)F1 mice showed strong Wnt‐inhibitory effects in vitro. Dkk‐1 concentrations comparable to those observed in lupus‐prone mice induced apoptosis in tubular and mesangial cells in vitro, whereas no such effect was seen for the range of concentrations observed in young prediseased mice and control BALB/c mice.
Conclusion
These data demonstrate that renal Wnt signaling activity is increased in lupus and is accompanied by an increase in renal and serum levels of Dkk‐1. The Wnt pathway is involved in the turnover of extracellular matrix constituents and represents a potential mediator of the morphologic changes that occur within the glomerulus during the development of nephritis. Furthermore, increased levels of Dkk‐1 serve as a potential proapoptotic stimulus in vitro and possibly in vivo and could be an important element in the initiation and progression of systemic and end‐organ disease manifestations in systemic lupus erythematosus.</description><identifier>ISSN: 0004-3591</identifier><identifier>ISSN: 2326-5191</identifier><identifier>EISSN: 1529-0131</identifier><identifier>EISSN: 2326-5205</identifier><identifier>DOI: 10.1002/art.30116</identifier><identifier>PMID: 21280006</identifier><identifier>CODEN: ARHEAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Antibodies, Antinuclear - analysis ; Apoptosis - drug effects ; beta Catenin - genetics ; beta Catenin - metabolism ; Biological and medical sciences ; Cells, Cultured ; Dermatology ; Disease Models, Animal ; Diseases of the osteoarticular system ; DNA - immunology ; Female ; Gene Expression ; Glomerular Mesangium - drug effects ; Glomerular Mesangium - pathology ; Humans ; Intercellular Signaling Peptides and Proteins - pharmacology ; Kidney - drug effects ; Kidney - metabolism ; Lupus Nephritis - genetics ; Lupus Nephritis - metabolism ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NZB ; Signal Transduction ; Skin involvement in other diseases. Miscellaneous. General aspects ; Wnt Proteins - genetics ; Wnt Proteins - metabolism</subject><ispartof>Arthritis & rheumatology (Hoboken, N.J.), 2011-02, Vol.63 (2), p.513-522</ispartof><rights>Copyright © 2011 by the American College of Rheumatology</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 by the American College of Rheumatology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4176-b1337fc7b47dd14075b5c2a84d8f39ab2587e1f57e9df9e99426f915284c50b43</citedby><cites>FETCH-LOGICAL-c4176-b1337fc7b47dd14075b5c2a84d8f39ab2587e1f57e9df9e99426f915284c50b43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fart.30116$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fart.30116$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23908328$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21280006$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tveita, Anders Aune</creatorcontrib><creatorcontrib>Rekvig, Ole Petter</creatorcontrib><title>Alterations in Wnt pathway activity in mouse serum and kidneys during lupus development</title><title>Arthritis & rheumatology (Hoboken, N.J.)</title><addtitle>Arthritis Rheum</addtitle><description>Objective
The canonical Wnt/β‐catenin pathway was recently identified as a factor in the pathogenesis of several renal diseases. The aim of this study was to evaluate Wnt signaling activity during disease development in a murine model of lupus nephritis.
Methods
Wnt activity and Dkk‐1 expression were serially assayed in the serum and kidneys of (NZB × NZW)F1 mice during progression of lupus nephritis. The effects of serum obtained from mice with lupus and serum‐equivalent concentrations of Dkk‐1 on mesangial cells were assessed in vitro.
Results
Gene expression analyses revealed increased canonical Wnt pathway activity in kidneys during development of lupus nephritis, paralleled by an increase in renal and serum levels of the Wnt inhibitor Dkk‐1. Sera obtained from proteinuric‐stage (NZB × NZW)F1 mice showed strong Wnt‐inhibitory effects in vitro. Dkk‐1 concentrations comparable to those observed in lupus‐prone mice induced apoptosis in tubular and mesangial cells in vitro, whereas no such effect was seen for the range of concentrations observed in young prediseased mice and control BALB/c mice.
Conclusion
These data demonstrate that renal Wnt signaling activity is increased in lupus and is accompanied by an increase in renal and serum levels of Dkk‐1. The Wnt pathway is involved in the turnover of extracellular matrix constituents and represents a potential mediator of the morphologic changes that occur within the glomerulus during the development of nephritis. Furthermore, increased levels of Dkk‐1 serve as a potential proapoptotic stimulus in vitro and possibly in vivo and could be an important element in the initiation and progression of systemic and end‐organ disease manifestations in systemic lupus erythematosus.</description><subject>Animals</subject><subject>Antibodies, Antinuclear - analysis</subject><subject>Apoptosis - drug effects</subject><subject>beta Catenin - genetics</subject><subject>beta Catenin - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cells, Cultured</subject><subject>Dermatology</subject><subject>Disease Models, Animal</subject><subject>Diseases of the osteoarticular system</subject><subject>DNA - immunology</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Glomerular Mesangium - drug effects</subject><subject>Glomerular Mesangium - pathology</subject><subject>Humans</subject><subject>Intercellular Signaling Peptides and Proteins - pharmacology</subject><subject>Kidney - drug effects</subject><subject>Kidney - metabolism</subject><subject>Lupus Nephritis - genetics</subject><subject>Lupus Nephritis - metabolism</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred NZB</subject><subject>Signal Transduction</subject><subject>Skin involvement in other diseases. Miscellaneous. General aspects</subject><subject>Wnt Proteins - genetics</subject><subject>Wnt Proteins - metabolism</subject><issn>0004-3591</issn><issn>2326-5191</issn><issn>1529-0131</issn><issn>2326-5205</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10EtrFTEUB_Agir1WF34BCYiIi2nznCTLS_EFBUEqXYZM5oymzmTGJNMy397Ue1UQXIUTfpzHH6HnlJxRQti5S-WME0rbB2hHJTMNoZw-RDtCiGi4NPQEPcn5ppaMS_4YnTDKdK3aHbrejwWSK2GOGYeIr2PBiyvf7tyGnS_hNpTt_n-a1ww4Q1on7GKPv4c-wpZxv6YQv-JxXdZawC2M8zJBLE_Ro8GNGZ4d31P05d3bq4sPzeWn9x8v9peNF1S1TUc5V4NXnVB9TwVRspOeOS16PXDjOia1AjpIBaYfDBgjWDuYeqMWXpJO8FP0-tB3SfOPFXKxU8gextFFqCtbLXSrFTesypf_yJt5TbEuZ6mkinDOmKnqzUH5NOecYLBLCpNLm6XE3odta9j2V9jVvjh2XLsJ-j_yd7oVvDoCl70bh-SiD_mv44ZoznR15wd3F0bY_j_R7j9fHUb_BE_glOo</recordid><startdate>201102</startdate><enddate>201102</enddate><creator>Tveita, Anders Aune</creator><creator>Rekvig, Ole Petter</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><general>Wiley Subscription Services, Inc</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>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201102</creationdate><title>Alterations in Wnt pathway activity in mouse serum and kidneys during lupus development</title><author>Tveita, Anders Aune ; Rekvig, Ole Petter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4176-b1337fc7b47dd14075b5c2a84d8f39ab2587e1f57e9df9e99426f915284c50b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Antibodies, Antinuclear - analysis</topic><topic>Apoptosis - drug effects</topic><topic>beta Catenin - genetics</topic><topic>beta Catenin - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cells, Cultured</topic><topic>Dermatology</topic><topic>Disease Models, Animal</topic><topic>Diseases of the osteoarticular system</topic><topic>DNA - immunology</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Glomerular Mesangium - drug effects</topic><topic>Glomerular Mesangium - pathology</topic><topic>Humans</topic><topic>Intercellular Signaling Peptides and Proteins - pharmacology</topic><topic>Kidney - drug effects</topic><topic>Kidney - metabolism</topic><topic>Lupus Nephritis - genetics</topic><topic>Lupus Nephritis - metabolism</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred NZB</topic><topic>Signal Transduction</topic><topic>Skin involvement in other diseases. Miscellaneous. General aspects</topic><topic>Wnt Proteins - genetics</topic><topic>Wnt Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tveita, Anders Aune</creatorcontrib><creatorcontrib>Rekvig, Ole Petter</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tveita, Anders Aune</au><au>Rekvig, Ole Petter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alterations in Wnt pathway activity in mouse serum and kidneys during lupus development</atitle><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle><addtitle>Arthritis Rheum</addtitle><date>2011-02</date><risdate>2011</risdate><volume>63</volume><issue>2</issue><spage>513</spage><epage>522</epage><pages>513-522</pages><issn>0004-3591</issn><issn>2326-5191</issn><eissn>1529-0131</eissn><eissn>2326-5205</eissn><coden>ARHEAW</coden><abstract>Objective
The canonical Wnt/β‐catenin pathway was recently identified as a factor in the pathogenesis of several renal diseases. The aim of this study was to evaluate Wnt signaling activity during disease development in a murine model of lupus nephritis.
Methods
Wnt activity and Dkk‐1 expression were serially assayed in the serum and kidneys of (NZB × NZW)F1 mice during progression of lupus nephritis. The effects of serum obtained from mice with lupus and serum‐equivalent concentrations of Dkk‐1 on mesangial cells were assessed in vitro.
Results
Gene expression analyses revealed increased canonical Wnt pathway activity in kidneys during development of lupus nephritis, paralleled by an increase in renal and serum levels of the Wnt inhibitor Dkk‐1. Sera obtained from proteinuric‐stage (NZB × NZW)F1 mice showed strong Wnt‐inhibitory effects in vitro. Dkk‐1 concentrations comparable to those observed in lupus‐prone mice induced apoptosis in tubular and mesangial cells in vitro, whereas no such effect was seen for the range of concentrations observed in young prediseased mice and control BALB/c mice.
Conclusion
These data demonstrate that renal Wnt signaling activity is increased in lupus and is accompanied by an increase in renal and serum levels of Dkk‐1. The Wnt pathway is involved in the turnover of extracellular matrix constituents and represents a potential mediator of the morphologic changes that occur within the glomerulus during the development of nephritis. Furthermore, increased levels of Dkk‐1 serve as a potential proapoptotic stimulus in vitro and possibly in vivo and could be an important element in the initiation and progression of systemic and end‐organ disease manifestations in systemic lupus erythematosus.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21280006</pmid><doi>10.1002/art.30116</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Arthritis & rheumatology (Hoboken, N.J.), 2011-02, Vol.63 (2), p.513-522 |
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| subjects | Animals Antibodies, Antinuclear - analysis Apoptosis - drug effects beta Catenin - genetics beta Catenin - metabolism Biological and medical sciences Cells, Cultured Dermatology Disease Models, Animal Diseases of the osteoarticular system DNA - immunology Female Gene Expression Glomerular Mesangium - drug effects Glomerular Mesangium - pathology Humans Intercellular Signaling Peptides and Proteins - pharmacology Kidney - drug effects Kidney - metabolism Lupus Nephritis - genetics Lupus Nephritis - metabolism Medical sciences Mice Mice, Inbred BALB C Mice, Inbred NZB Signal Transduction Skin involvement in other diseases. Miscellaneous. General aspects Wnt Proteins - genetics Wnt Proteins - metabolism |
| title | Alterations in Wnt pathway activity in mouse serum and kidneys during lupus development |
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