Genome-Wide Gene Expression Profiling of Randall's Plaques in Calcium Oxalate Stone Formers
Randall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discov...
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| Veröffentlicht in: | Journal of the American Society of Nephrology 2017-01, Vol.28 (1), p.333-347 |
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| creator | Taguchi, Kazumi Hamamoto, Shuzo Okada, Atsushi Unno, Rei Kamisawa, Hideyuki Naiki, Taku Ando, Ryosuke Mizuno, Kentaro Kawai, Noriyasu Tozawa, Keiichi Kohri, Kenjiro Yasui, Takahiro |
| description | Randall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (˃2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P |
| doi_str_mv | 10.1681/ASN.2015111271 |
| format | Article |
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We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (˃2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P<0.01). In network and toxicity analyses, these genes associated with activated mitogen-activated protein kinase, the Akt/phosphatidylinositol 3-kinase pathway, and proinflammatory cytokines that cause renal injury and oxidative stress. Additionally, expression of proinflammatory cytokines, numbers of immune cells, and cellular apoptosis increased in RP tissue. This study establishes an association between genes related to renal dysfunction, proinflammation, oxidative stress, and ion transport and RP development in CaOx SFs.</description><identifier>ISSN: 1046-6673</identifier><identifier>EISSN: 1533-3450</identifier><identifier>DOI: 10.1681/ASN.2015111271</identifier><identifier>PMID: 27297950</identifier><language>eng</language><publisher>United States: American Society of Nephrology</publisher><subject>Calcium Oxalate - metabolism ; Clinical Research ; Female ; Gene Expression Profiling ; Genome-Wide Association Study ; Humans ; Kidney Calculi - genetics ; Kidney Calculi - surgery ; Kidney Medulla - metabolism ; Male ; Middle Aged</subject><ispartof>Journal of the American Society of Nephrology, 2017-01, Vol.28 (1), p.333-347</ispartof><rights>Copyright © 2016 by the American Society of Nephrology.</rights><rights>Copyright © 2016 by the American Society of Nephrology 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c501t-d91b63a0ec0652a74602b451320c0010cb2b50d827a934280f2a450021e68bb13</citedby><cites>FETCH-LOGICAL-c501t-d91b63a0ec0652a74602b451320c0010cb2b50d827a934280f2a450021e68bb13</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/PMC5198277/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198277/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27297950$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Taguchi, Kazumi</creatorcontrib><creatorcontrib>Hamamoto, Shuzo</creatorcontrib><creatorcontrib>Okada, Atsushi</creatorcontrib><creatorcontrib>Unno, Rei</creatorcontrib><creatorcontrib>Kamisawa, Hideyuki</creatorcontrib><creatorcontrib>Naiki, Taku</creatorcontrib><creatorcontrib>Ando, Ryosuke</creatorcontrib><creatorcontrib>Mizuno, Kentaro</creatorcontrib><creatorcontrib>Kawai, Noriyasu</creatorcontrib><creatorcontrib>Tozawa, Keiichi</creatorcontrib><creatorcontrib>Kohri, Kenjiro</creatorcontrib><creatorcontrib>Yasui, Takahiro</creatorcontrib><title>Genome-Wide Gene Expression Profiling of Randall's Plaques in Calcium Oxalate Stone Formers</title><title>Journal of the American Society of Nephrology</title><addtitle>J Am Soc Nephrol</addtitle><description>Randall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (˃2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P<0.01). In network and toxicity analyses, these genes associated with activated mitogen-activated protein kinase, the Akt/phosphatidylinositol 3-kinase pathway, and proinflammatory cytokines that cause renal injury and oxidative stress. Additionally, expression of proinflammatory cytokines, numbers of immune cells, and cellular apoptosis increased in RP tissue. This study establishes an association between genes related to renal dysfunction, proinflammation, oxidative stress, and ion transport and RP development in CaOx SFs.</description><subject>Calcium Oxalate - metabolism</subject><subject>Clinical Research</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Kidney Calculi - genetics</subject><subject>Kidney Calculi - surgery</subject><subject>Kidney Medulla - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><issn>1046-6673</issn><issn>1533-3450</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUFP3DAQha2qCCjl2mPlW3vJMmPHdnKphFawICFABcSBg-UkztaVEy92tqL_HqPdUjjNSPPmmzd6hHxBmKGs8Oj45nLGAAUiMoUfyD4KzgteCviYeyhlIaXie-RTSr8h65hSu2SPKVarWsA-eVjYMQy2uHedpbm39ORpFW1KLoz0OobeeTcuaejpTzN2xvtviV5787i2ibqRzo1v3XqgV0_Gm8nSmylkxGmIg43pM9npjU_2cFsPyN3pye38rLi4WpzPjy-KVgBORVdjI7kB24IUzKhSAmtKgZxBmy1D27BGQFcxZWpesgp6ZvJ_wNDKqmmQH5AfG-5q3Qy2a-04ReP1KrrBxL86GKffT0b3Sy_DHy2wzlSVAd-3gBhePpv04FJrvTejDeuksWJSAXBgWTrbSNsYUoq2fz2DoF8S0TkR_T-RvPD1rblX-b8I-DOmGYXQ</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>Taguchi, Kazumi</creator><creator>Hamamoto, Shuzo</creator><creator>Okada, Atsushi</creator><creator>Unno, Rei</creator><creator>Kamisawa, Hideyuki</creator><creator>Naiki, Taku</creator><creator>Ando, Ryosuke</creator><creator>Mizuno, Kentaro</creator><creator>Kawai, Noriyasu</creator><creator>Tozawa, Keiichi</creator><creator>Kohri, Kenjiro</creator><creator>Yasui, Takahiro</creator><general>American Society of Nephrology</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>20170101</creationdate><title>Genome-Wide Gene Expression Profiling of Randall's Plaques in Calcium Oxalate Stone Formers</title><author>Taguchi, Kazumi ; Hamamoto, Shuzo ; Okada, Atsushi ; Unno, Rei ; Kamisawa, Hideyuki ; Naiki, Taku ; Ando, Ryosuke ; Mizuno, Kentaro ; Kawai, Noriyasu ; Tozawa, Keiichi ; Kohri, Kenjiro ; Yasui, Takahiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c501t-d91b63a0ec0652a74602b451320c0010cb2b50d827a934280f2a450021e68bb13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Calcium Oxalate - metabolism</topic><topic>Clinical Research</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Kidney Calculi - genetics</topic><topic>Kidney Calculi - surgery</topic><topic>Kidney Medulla - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Taguchi, Kazumi</creatorcontrib><creatorcontrib>Hamamoto, Shuzo</creatorcontrib><creatorcontrib>Okada, Atsushi</creatorcontrib><creatorcontrib>Unno, Rei</creatorcontrib><creatorcontrib>Kamisawa, Hideyuki</creatorcontrib><creatorcontrib>Naiki, Taku</creatorcontrib><creatorcontrib>Ando, Ryosuke</creatorcontrib><creatorcontrib>Mizuno, Kentaro</creatorcontrib><creatorcontrib>Kawai, Noriyasu</creatorcontrib><creatorcontrib>Tozawa, Keiichi</creatorcontrib><creatorcontrib>Kohri, Kenjiro</creatorcontrib><creatorcontrib>Yasui, Takahiro</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>Journal of the American Society of Nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Taguchi, Kazumi</au><au>Hamamoto, Shuzo</au><au>Okada, Atsushi</au><au>Unno, Rei</au><au>Kamisawa, Hideyuki</au><au>Naiki, Taku</au><au>Ando, Ryosuke</au><au>Mizuno, Kentaro</au><au>Kawai, Noriyasu</au><au>Tozawa, Keiichi</au><au>Kohri, Kenjiro</au><au>Yasui, Takahiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-Wide Gene Expression Profiling of Randall's Plaques in Calcium Oxalate Stone Formers</atitle><jtitle>Journal of the American Society of Nephrology</jtitle><addtitle>J Am Soc Nephrol</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>28</volume><issue>1</issue><spage>333</spage><epage>347</epage><pages>333-347</pages><issn>1046-6673</issn><eissn>1533-3450</eissn><abstract>Randall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (˃2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P<0.01). In network and toxicity analyses, these genes associated with activated mitogen-activated protein kinase, the Akt/phosphatidylinositol 3-kinase pathway, and proinflammatory cytokines that cause renal injury and oxidative stress. Additionally, expression of proinflammatory cytokines, numbers of immune cells, and cellular apoptosis increased in RP tissue. This study establishes an association between genes related to renal dysfunction, proinflammation, oxidative stress, and ion transport and RP development in CaOx SFs.</abstract><cop>United States</cop><pub>American Society of Nephrology</pub><pmid>27297950</pmid><doi>10.1681/ASN.2015111271</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Calcium Oxalate - metabolism Clinical Research Female Gene Expression Profiling Genome-Wide Association Study Humans Kidney Calculi - genetics Kidney Calculi - surgery Kidney Medulla - metabolism Male Middle Aged |
| title | Genome-Wide Gene Expression Profiling of Randall's Plaques in Calcium Oxalate Stone Formers |
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