Uric acid activates NRLP3 inflammasome in an in-vivo model of epithelial to mesenchymal transition in the kidney
Uric acid (UA) has been associated with renal fibrosis and progression of chronic kidney disease. However, the underlying mechanisms of this process have still not been identified. Here, we studied the role of the innate imunity receptor NLRP3/ASC in UA induced epithelial-mesenchymal transition (EMT...
Gespeichert in:
| Veröffentlicht in: | Journal of molecular histology 2017-06, Vol.48 (3), p.209-218 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 218 |
|---|---|
| container_issue | 3 |
| container_start_page | 209 |
| container_title | Journal of molecular histology |
| container_volume | 48 |
| creator | Romero, César Andrés Remor, Aline Latini, Alexandra De Paul, Ana Lucía Torres, Alicia Inés Mukdsi, Jorge Humberto |
| description | Uric acid (UA) has been associated with renal fibrosis and progression of chronic kidney disease. However, the underlying mechanisms of this process have still not been identified. Here, we studied the role of the innate imunity receptor NLRP3/ASC in UA induced epithelial-mesenchymal transition (EMT) in kidney. Wistar rats were fed with oxonic acid 2% and UA 2% (OXA + U), OXA + U plus allopurinol (ALL) or regular chow (C) for 7 weeks. We analyzed the presence of EMT markers, the expression of NLRP3, ASC, Caspase-1 and Smad 2/3 molecules and the mitochondrial morphological and functional characteristics. High UA induced renal fibrosis, mild chronic inflammation, as well as morphological and biochemical evidence of EMT. High UA also increased the expression of NLRP3/ASC with activation of both inflammasome related caspase-1 and inflammasome unrelated Smad 2/3 pathways. Ultrastructural co-localization of NLRP3 and Smad 2/3 indicated physical interaction between the two molecules. No morphological or functional changes were found between mitochondria exposed to high UA. In conclusion, kidney epithelial NLRP3/ASC expression was increased in high UA state in rats and both inflammasome related caspase-1 and non-inflammasome related P-Smad 2/3 pathways were associated with the observed EMT, inflammation and fibrosis induced by UA in the kidney. |
| doi_str_mv | 10.1007/s10735-017-9720-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1884166801</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1884166801</sourcerecordid><originalsourceid>FETCH-LOGICAL-c438t-9e7e2cd485fed9cd77f6f4143aaaf9171c82155215b5af3cc9c630a94e8305a23</originalsourceid><addsrcrecordid>eNp1kU1LAzEQhoMotn78AC8S8OJlNR-7m-QoxS8oKqLnELMTTd3d1GRb6L83pSoieMhkJnlmEt4XoSNKzigh4jxRInhVECoKJRgp1BYa06oWBeNSbP_kQo3QXkozQpisS7WLRkxyUdKKjdH8OXqLjfVNDoNfmgESvnucPnDse9earjMpdJALbPoci6VfBtyFBlocHIa5H96g9abFQz6GBL19W3XrMpo--cGHdRfOEH73TQ-rA7TjTJvg8GvfR89Xl0-Tm2J6f307uZgWtuRyKBQIYLYpZeWgUbYRwtWupCU3xjhFBbWS0arK66UyjlurbM2JUSVITirD-D463cydx_CxgDTozicLbWt6CIukqZQlrWtJaEZP_qCzsIh9_l2mVFaWZj0zRTeUjSGlCE7Po-9MXGlK9NoOvbFDZzv02g6tcs_x1-TFSwfNT8e3_hlgGyDlq_4V4q-n_536CVltlUw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1899721238</pqid></control><display><type>article</type><title>Uric acid activates NRLP3 inflammasome in an in-vivo model of epithelial to mesenchymal transition in the kidney</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Romero, César Andrés ; Remor, Aline ; Latini, Alexandra ; De Paul, Ana Lucía ; Torres, Alicia Inés ; Mukdsi, Jorge Humberto</creator><creatorcontrib>Romero, César Andrés ; Remor, Aline ; Latini, Alexandra ; De Paul, Ana Lucía ; Torres, Alicia Inés ; Mukdsi, Jorge Humberto</creatorcontrib><description>Uric acid (UA) has been associated with renal fibrosis and progression of chronic kidney disease. However, the underlying mechanisms of this process have still not been identified. Here, we studied the role of the innate imunity receptor NLRP3/ASC in UA induced epithelial-mesenchymal transition (EMT) in kidney. Wistar rats were fed with oxonic acid 2% and UA 2% (OXA + U), OXA + U plus allopurinol (ALL) or regular chow (C) for 7 weeks. We analyzed the presence of EMT markers, the expression of NLRP3, ASC, Caspase-1 and Smad 2/3 molecules and the mitochondrial morphological and functional characteristics. High UA induced renal fibrosis, mild chronic inflammation, as well as morphological and biochemical evidence of EMT. High UA also increased the expression of NLRP3/ASC with activation of both inflammasome related caspase-1 and inflammasome unrelated Smad 2/3 pathways. Ultrastructural co-localization of NLRP3 and Smad 2/3 indicated physical interaction between the two molecules. No morphological or functional changes were found between mitochondria exposed to high UA. In conclusion, kidney epithelial NLRP3/ASC expression was increased in high UA state in rats and both inflammasome related caspase-1 and non-inflammasome related P-Smad 2/3 pathways were associated with the observed EMT, inflammation and fibrosis induced by UA in the kidney.</description><identifier>ISSN: 1567-2379</identifier><identifier>EISSN: 1567-2387</identifier><identifier>DOI: 10.1007/s10735-017-9720-9</identifier><identifier>PMID: 28374152</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Allopurinol ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Caspase ; Caspase 1 - metabolism ; Caspase-1 ; Cell Biology ; Developmental Biology ; Epithelial-Mesenchymal Transition - drug effects ; Fibrosis ; Fibrosis - chemically induced ; Inflammasomes ; Inflammasomes - metabolism ; Inflammation - chemically induced ; Kidney Diseases - metabolism ; Life Sciences ; Localization ; Male ; Mesenchyme ; Mitochondria ; Morphology ; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism ; Original Paper ; Physical characteristics ; Rats, Wistar ; Rodents ; Smad protein ; Smad Proteins - metabolism ; Uric acid ; Uric Acid - pharmacology</subject><ispartof>Journal of molecular histology, 2017-06, Vol.48 (3), p.209-218</ispartof><rights>Springer Science+Business Media Dordrecht 2017</rights><rights>Journal of Molecular Histology is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-9e7e2cd485fed9cd77f6f4143aaaf9171c82155215b5af3cc9c630a94e8305a23</citedby><cites>FETCH-LOGICAL-c438t-9e7e2cd485fed9cd77f6f4143aaaf9171c82155215b5af3cc9c630a94e8305a23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10735-017-9720-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10735-017-9720-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28374152$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Romero, César Andrés</creatorcontrib><creatorcontrib>Remor, Aline</creatorcontrib><creatorcontrib>Latini, Alexandra</creatorcontrib><creatorcontrib>De Paul, Ana Lucía</creatorcontrib><creatorcontrib>Torres, Alicia Inés</creatorcontrib><creatorcontrib>Mukdsi, Jorge Humberto</creatorcontrib><title>Uric acid activates NRLP3 inflammasome in an in-vivo model of epithelial to mesenchymal transition in the kidney</title><title>Journal of molecular histology</title><addtitle>J Mol Hist</addtitle><addtitle>J Mol Histol</addtitle><description>Uric acid (UA) has been associated with renal fibrosis and progression of chronic kidney disease. However, the underlying mechanisms of this process have still not been identified. Here, we studied the role of the innate imunity receptor NLRP3/ASC in UA induced epithelial-mesenchymal transition (EMT) in kidney. Wistar rats were fed with oxonic acid 2% and UA 2% (OXA + U), OXA + U plus allopurinol (ALL) or regular chow (C) for 7 weeks. We analyzed the presence of EMT markers, the expression of NLRP3, ASC, Caspase-1 and Smad 2/3 molecules and the mitochondrial morphological and functional characteristics. High UA induced renal fibrosis, mild chronic inflammation, as well as morphological and biochemical evidence of EMT. High UA also increased the expression of NLRP3/ASC with activation of both inflammasome related caspase-1 and inflammasome unrelated Smad 2/3 pathways. Ultrastructural co-localization of NLRP3 and Smad 2/3 indicated physical interaction between the two molecules. No morphological or functional changes were found between mitochondria exposed to high UA. In conclusion, kidney epithelial NLRP3/ASC expression was increased in high UA state in rats and both inflammasome related caspase-1 and non-inflammasome related P-Smad 2/3 pathways were associated with the observed EMT, inflammation and fibrosis induced by UA in the kidney.</description><subject>Allopurinol</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Caspase</subject><subject>Caspase 1 - metabolism</subject><subject>Caspase-1</subject><subject>Cell Biology</subject><subject>Developmental Biology</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Fibrosis</subject><subject>Fibrosis - chemically induced</subject><subject>Inflammasomes</subject><subject>Inflammasomes - metabolism</subject><subject>Inflammation - chemically induced</subject><subject>Kidney Diseases - metabolism</subject><subject>Life Sciences</subject><subject>Localization</subject><subject>Male</subject><subject>Mesenchyme</subject><subject>Mitochondria</subject><subject>Morphology</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</subject><subject>Original Paper</subject><subject>Physical characteristics</subject><subject>Rats, Wistar</subject><subject>Rodents</subject><subject>Smad protein</subject><subject>Smad Proteins - metabolism</subject><subject>Uric acid</subject><subject>Uric Acid - pharmacology</subject><issn>1567-2379</issn><issn>1567-2387</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kU1LAzEQhoMotn78AC8S8OJlNR-7m-QoxS8oKqLnELMTTd3d1GRb6L83pSoieMhkJnlmEt4XoSNKzigh4jxRInhVECoKJRgp1BYa06oWBeNSbP_kQo3QXkozQpisS7WLRkxyUdKKjdH8OXqLjfVNDoNfmgESvnucPnDse9earjMpdJALbPoci6VfBtyFBlocHIa5H96g9abFQz6GBL19W3XrMpo--cGHdRfOEH73TQ-rA7TjTJvg8GvfR89Xl0-Tm2J6f307uZgWtuRyKBQIYLYpZeWgUbYRwtWupCU3xjhFBbWS0arK66UyjlurbM2JUSVITirD-D463cydx_CxgDTozicLbWt6CIukqZQlrWtJaEZP_qCzsIh9_l2mVFaWZj0zRTeUjSGlCE7Po-9MXGlK9NoOvbFDZzv02g6tcs_x1-TFSwfNT8e3_hlgGyDlq_4V4q-n_536CVltlUw</recordid><startdate>20170601</startdate><enddate>20170601</enddate><creator>Romero, César Andrés</creator><creator>Remor, Aline</creator><creator>Latini, Alexandra</creator><creator>De Paul, Ana Lucía</creator><creator>Torres, Alicia Inés</creator><creator>Mukdsi, Jorge Humberto</creator><general>Springer Netherlands</general><general>Springer Nature B.V</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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</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>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20170601</creationdate><title>Uric acid activates NRLP3 inflammasome in an in-vivo model of epithelial to mesenchymal transition in the kidney</title><author>Romero, César Andrés ; Remor, Aline ; Latini, Alexandra ; De Paul, Ana Lucía ; Torres, Alicia Inés ; Mukdsi, Jorge Humberto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-9e7e2cd485fed9cd77f6f4143aaaf9171c82155215b5af3cc9c630a94e8305a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Allopurinol</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Caspase</topic><topic>Caspase 1 - metabolism</topic><topic>Caspase-1</topic><topic>Cell Biology</topic><topic>Developmental Biology</topic><topic>Epithelial-Mesenchymal Transition - drug effects</topic><topic>Fibrosis</topic><topic>Fibrosis - chemically induced</topic><topic>Inflammasomes</topic><topic>Inflammasomes - metabolism</topic><topic>Inflammation - chemically induced</topic><topic>Kidney Diseases - metabolism</topic><topic>Life Sciences</topic><topic>Localization</topic><topic>Male</topic><topic>Mesenchyme</topic><topic>Mitochondria</topic><topic>Morphology</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</topic><topic>Original Paper</topic><topic>Physical characteristics</topic><topic>Rats, Wistar</topic><topic>Rodents</topic><topic>Smad protein</topic><topic>Smad Proteins - metabolism</topic><topic>Uric acid</topic><topic>Uric Acid - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Romero, César Andrés</creatorcontrib><creatorcontrib>Remor, Aline</creatorcontrib><creatorcontrib>Latini, Alexandra</creatorcontrib><creatorcontrib>De Paul, Ana Lucía</creatorcontrib><creatorcontrib>Torres, Alicia Inés</creatorcontrib><creatorcontrib>Mukdsi, Jorge Humberto</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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 (ProQuest)</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>MEDLINE - Academic</collection><jtitle>Journal of molecular histology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Romero, César Andrés</au><au>Remor, Aline</au><au>Latini, Alexandra</au><au>De Paul, Ana Lucía</au><au>Torres, Alicia Inés</au><au>Mukdsi, Jorge Humberto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Uric acid activates NRLP3 inflammasome in an in-vivo model of epithelial to mesenchymal transition in the kidney</atitle><jtitle>Journal of molecular histology</jtitle><stitle>J Mol Hist</stitle><addtitle>J Mol Histol</addtitle><date>2017-06-01</date><risdate>2017</risdate><volume>48</volume><issue>3</issue><spage>209</spage><epage>218</epage><pages>209-218</pages><issn>1567-2379</issn><eissn>1567-2387</eissn><abstract>Uric acid (UA) has been associated with renal fibrosis and progression of chronic kidney disease. However, the underlying mechanisms of this process have still not been identified. Here, we studied the role of the innate imunity receptor NLRP3/ASC in UA induced epithelial-mesenchymal transition (EMT) in kidney. Wistar rats were fed with oxonic acid 2% and UA 2% (OXA + U), OXA + U plus allopurinol (ALL) or regular chow (C) for 7 weeks. We analyzed the presence of EMT markers, the expression of NLRP3, ASC, Caspase-1 and Smad 2/3 molecules and the mitochondrial morphological and functional characteristics. High UA induced renal fibrosis, mild chronic inflammation, as well as morphological and biochemical evidence of EMT. High UA also increased the expression of NLRP3/ASC with activation of both inflammasome related caspase-1 and inflammasome unrelated Smad 2/3 pathways. Ultrastructural co-localization of NLRP3 and Smad 2/3 indicated physical interaction between the two molecules. No morphological or functional changes were found between mitochondria exposed to high UA. In conclusion, kidney epithelial NLRP3/ASC expression was increased in high UA state in rats and both inflammasome related caspase-1 and non-inflammasome related P-Smad 2/3 pathways were associated with the observed EMT, inflammation and fibrosis induced by UA in the kidney.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>28374152</pmid><doi>10.1007/s10735-017-9720-9</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1567-2379 |
| ispartof | Journal of molecular histology, 2017-06, Vol.48 (3), p.209-218 |
| issn | 1567-2379 1567-2387 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1884166801 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Allopurinol Animals Biomedical and Life Sciences Biomedicine Caspase Caspase 1 - metabolism Caspase-1 Cell Biology Developmental Biology Epithelial-Mesenchymal Transition - drug effects Fibrosis Fibrosis - chemically induced Inflammasomes Inflammasomes - metabolism Inflammation - chemically induced Kidney Diseases - metabolism Life Sciences Localization Male Mesenchyme Mitochondria Morphology NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Original Paper Physical characteristics Rats, Wistar Rodents Smad protein Smad Proteins - metabolism Uric acid Uric Acid - pharmacology |
| title | Uric acid activates NRLP3 inflammasome in an in-vivo model of epithelial to mesenchymal transition in the kidney |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T12%3A35%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Uric%20acid%20activates%20NRLP3%20inflammasome%20in%20an%20in-vivo%20model%20of%20epithelial%20to%20mesenchymal%20transition%20in%20the%20kidney&rft.jtitle=Journal%20of%20molecular%20histology&rft.au=Romero,%20C%C3%A9sar%20Andr%C3%A9s&rft.date=2017-06-01&rft.volume=48&rft.issue=3&rft.spage=209&rft.epage=218&rft.pages=209-218&rft.issn=1567-2379&rft.eissn=1567-2387&rft_id=info:doi/10.1007/s10735-017-9720-9&rft_dat=%3Cproquest_cross%3E1884166801%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1899721238&rft_id=info:pmid/28374152&rfr_iscdi=true |