Increased Urinary Exosomal MicroRNAs in Patients with Systemic Lupus Erythematosus
There is increased interest in using microRNAs (miRNAs) as biomarkers in different diseases. Present in body fluids, it is controversial whether or not they are mainly enclosed in exosomes, thus we studied if urinary miRNAs are concentrated inside exosomes and if the presence of systemic lupus eryth...
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| Veröffentlicht in: | PloS one 2015-09, Vol.10 (9), p.e0138618-e0138618 |
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| creator | Perez-Hernandez, Javier Forner, Maria J Pinto, Carolina Chaves, Felipe J Cortes, Raquel Redon, Josep |
| description | There is increased interest in using microRNAs (miRNAs) as biomarkers in different diseases. Present in body fluids, it is controversial whether or not they are mainly enclosed in exosomes, thus we studied if urinary miRNAs are concentrated inside exosomes and if the presence of systemic lupus erythematosus with or without lupus nephritis modifies their distribution pattern. We quantified specific miRNAs in urine of patients with systemic lupus erythematosus (n = 38) and healthy controls (n = 12) by quantitative reverse-transcription PCR in cell-free urine, exosome-depleted supernatant and exosome pellet obtained by ultracentrifugation. In control group, miR-335* and miR-302d were consistently higher in exosomes than in exosome-depleted supernatant, and miR-200c and miR-146a were higher in cell-free fraction. In lupus patients, all urinary miRNAs tested were mainly in exosomes with lower levels outside them (p |
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Lucrecia</contributor><creatorcontrib>Perez-Hernandez, Javier ; Forner, Maria J ; Pinto, Carolina ; Chaves, Felipe J ; Cortes, Raquel ; Redon, Josep ; Alvarez, M. Lucrecia</creatorcontrib><description>There is increased interest in using microRNAs (miRNAs) as biomarkers in different diseases. Present in body fluids, it is controversial whether or not they are mainly enclosed in exosomes, thus we studied if urinary miRNAs are concentrated inside exosomes and if the presence of systemic lupus erythematosus with or without lupus nephritis modifies their distribution pattern. We quantified specific miRNAs in urine of patients with systemic lupus erythematosus (n = 38) and healthy controls (n = 12) by quantitative reverse-transcription PCR in cell-free urine, exosome-depleted supernatant and exosome pellet obtained by ultracentrifugation. In control group, miR-335* and miR-302d were consistently higher in exosomes than in exosome-depleted supernatant, and miR-200c and miR-146a were higher in cell-free fraction. In lupus patients, all urinary miRNAs tested were mainly in exosomes with lower levels outside them (p<0.05 and p<0.01, respectively). This pattern is especially relevant in patients with active lupus nephritis compared to the control group or to the SLE patients in absence of lupus nephritis, with miR-146a being the most augmented (100-fold change, p<0.001). Among the exosomal miRNAs tested, only the miR-146a discriminates the presence of active lupus nephritis. In conclusion, urinary miRNAs are contained primarily in exosomes in systemic lupus erythematosus, and the main increment was found in the presence of active lupus nephritis. These findings underscore the attractiveness of exosomal miRNAs in urine, a non-invasive method, as potential renal disease markers.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0138618</identifier><identifier>PMID: 26390437</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Autoimmune diseases ; Biological markers ; Biomarkers ; Biomarkers - urine ; Biomedical research ; Blood ; Body fluids ; Cancer ; Case-Control Studies ; Chronic conditions ; Diabetes ; Exosomes ; Exosomes - metabolism ; Female ; Gene expression ; Genetic aspects ; Humans ; Kidney diseases ; Lupus ; Lupus Erythematosus, Systemic - urine ; Lupus nephritis ; Lupus Nephritis - metabolism ; Lupus Nephritis - urine ; Male ; MicroRNA ; MicroRNAs ; MicroRNAs - urine ; Middle Aged ; miRNA ; Nephritis ; Nutrition ; Obesity ; Patients ; Systemic lupus erythematosus ; Transfer RNA ; Ultracentrifugation ; Urine</subject><ispartof>PloS one, 2015-09, Vol.10 (9), p.e0138618-e0138618</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Perez-Hernandez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Perez-Hernandez et al 2015 Perez-Hernandez et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-bee3a52ab473ab56ce6d13024eb8ff1262976497fc357d2b41c767c58fbdc7933</citedby><cites>FETCH-LOGICAL-c692t-bee3a52ab473ab56ce6d13024eb8ff1262976497fc357d2b41c767c58fbdc7933</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/PMC4577109/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577109/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26390437$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Alvarez, M. Lucrecia</contributor><creatorcontrib>Perez-Hernandez, Javier</creatorcontrib><creatorcontrib>Forner, Maria J</creatorcontrib><creatorcontrib>Pinto, Carolina</creatorcontrib><creatorcontrib>Chaves, Felipe J</creatorcontrib><creatorcontrib>Cortes, Raquel</creatorcontrib><creatorcontrib>Redon, Josep</creatorcontrib><title>Increased Urinary Exosomal MicroRNAs in Patients with Systemic Lupus Erythematosus</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>There is increased interest in using microRNAs (miRNAs) as biomarkers in different diseases. Present in body fluids, it is controversial whether or not they are mainly enclosed in exosomes, thus we studied if urinary miRNAs are concentrated inside exosomes and if the presence of systemic lupus erythematosus with or without lupus nephritis modifies their distribution pattern. We quantified specific miRNAs in urine of patients with systemic lupus erythematosus (n = 38) and healthy controls (n = 12) by quantitative reverse-transcription PCR in cell-free urine, exosome-depleted supernatant and exosome pellet obtained by ultracentrifugation. In control group, miR-335* and miR-302d were consistently higher in exosomes than in exosome-depleted supernatant, and miR-200c and miR-146a were higher in cell-free fraction. In lupus patients, all urinary miRNAs tested were mainly in exosomes with lower levels outside them (p<0.05 and p<0.01, respectively). This pattern is especially relevant in patients with active lupus nephritis compared to the control group or to the SLE patients in absence of lupus nephritis, with miR-146a being the most augmented (100-fold change, p<0.001). Among the exosomal miRNAs tested, only the miR-146a discriminates the presence of active lupus nephritis. In conclusion, urinary miRNAs are contained primarily in exosomes in systemic lupus erythematosus, and the main increment was found in the presence of active lupus nephritis. These findings underscore the attractiveness of exosomal miRNAs in urine, a non-invasive method, as potential renal disease markers.</description><subject>Adult</subject><subject>Autoimmune diseases</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Biomarkers - urine</subject><subject>Biomedical research</subject><subject>Blood</subject><subject>Body fluids</subject><subject>Cancer</subject><subject>Case-Control Studies</subject><subject>Chronic conditions</subject><subject>Diabetes</subject><subject>Exosomes</subject><subject>Exosomes - metabolism</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Humans</subject><subject>Kidney diseases</subject><subject>Lupus</subject><subject>Lupus Erythematosus, Systemic - urine</subject><subject>Lupus nephritis</subject><subject>Lupus Nephritis - metabolism</subject><subject>Lupus Nephritis - urine</subject><subject>Male</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - urine</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Nephritis</subject><subject>Nutrition</subject><subject>Obesity</subject><subject>Patients</subject><subject>Systemic lupus erythematosus</subject><subject>Transfer RNA</subject><subject>Ultracentrifugation</subject><subject>Urine</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</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><sourceid>DOA</sourceid><recordid>eNqNkl1v0zAUhiMEYqPwDxBEQkJw0eKv2PENUjUVqFQY6hi3luM4jaskLrYD67_HXbOpQbtAvrBlP-c9Pue8SfISghnEDH7Y2t51spntbKdnAOKcwvxRcg45RlOKAH58cj5Lnnm_BSCLFH2anCGKOSCYnSfrZaecll6X6bUznXT7dHFjvW1lk341ytn1t7lPTZd-l8HoLvj0jwl1erX3QbdGpat-1_t04fah1q0M1vf-efKkko3XL4Z9klx_Wvy4-DJdXX5eXsxXU0U5CtNCaywzJAvCsCwyqjQtIQaI6CKvKogo4owSziqFM1aigkDFKFNZXhWlYhzjSfL6qLtrrBdDO7yADHKUc0JZJJZHorRyK3bOtLE-YaURtxfWbYR0wahGiwKUOJcIaM4lIVXJK61LTIsiz5ECPI9aH4dsfdHqUsVeONmMRMcvnanFxv4WJGMMAh4F3g0Czv7qtQ-iNV7pppGdtv3tvyknAMfZTJI3_6APVzdQGxkLMF1lY151EBVzgjjOMKQwUrMHqLjKw_yidyoT70cB70cBkQn6Jmxk771YXq3_n738OWbfnrC1lk2ovW36YGznxyA5gtF93jtd3TcZAnGw_l03xMH6YrB-DHt1OqD7oDuv47-qIP6M</recordid><startdate>20150921</startdate><enddate>20150921</enddate><creator>Perez-Hernandez, Javier</creator><creator>Forner, Maria J</creator><creator>Pinto, Carolina</creator><creator>Chaves, Felipe J</creator><creator>Cortes, Raquel</creator><creator>Redon, Josep</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150921</creationdate><title>Increased Urinary Exosomal MicroRNAs in Patients with Systemic Lupus Erythematosus</title><author>Perez-Hernandez, Javier ; Forner, Maria J ; Pinto, Carolina ; Chaves, Felipe J ; Cortes, Raquel ; Redon, Josep</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-bee3a52ab473ab56ce6d13024eb8ff1262976497fc357d2b41c767c58fbdc7933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Autoimmune diseases</topic><topic>Biological markers</topic><topic>Biomarkers</topic><topic>Biomarkers - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Perez-Hernandez, Javier</au><au>Forner, Maria J</au><au>Pinto, Carolina</au><au>Chaves, Felipe J</au><au>Cortes, Raquel</au><au>Redon, Josep</au><au>Alvarez, M. Lucrecia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased Urinary Exosomal MicroRNAs in Patients with Systemic Lupus Erythematosus</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-09-21</date><risdate>2015</risdate><volume>10</volume><issue>9</issue><spage>e0138618</spage><epage>e0138618</epage><pages>e0138618-e0138618</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>There is increased interest in using microRNAs (miRNAs) as biomarkers in different diseases. Present in body fluids, it is controversial whether or not they are mainly enclosed in exosomes, thus we studied if urinary miRNAs are concentrated inside exosomes and if the presence of systemic lupus erythematosus with or without lupus nephritis modifies their distribution pattern. We quantified specific miRNAs in urine of patients with systemic lupus erythematosus (n = 38) and healthy controls (n = 12) by quantitative reverse-transcription PCR in cell-free urine, exosome-depleted supernatant and exosome pellet obtained by ultracentrifugation. In control group, miR-335* and miR-302d were consistently higher in exosomes than in exosome-depleted supernatant, and miR-200c and miR-146a were higher in cell-free fraction. In lupus patients, all urinary miRNAs tested were mainly in exosomes with lower levels outside them (p<0.05 and p<0.01, respectively). This pattern is especially relevant in patients with active lupus nephritis compared to the control group or to the SLE patients in absence of lupus nephritis, with miR-146a being the most augmented (100-fold change, p<0.001). Among the exosomal miRNAs tested, only the miR-146a discriminates the presence of active lupus nephritis. In conclusion, urinary miRNAs are contained primarily in exosomes in systemic lupus erythematosus, and the main increment was found in the presence of active lupus nephritis. These findings underscore the attractiveness of exosomal miRNAs in urine, a non-invasive method, as potential renal disease markers.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26390437</pmid><doi>10.1371/journal.pone.0138618</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Autoimmune diseases Biological markers Biomarkers Biomarkers - urine Biomedical research Blood Body fluids Cancer Case-Control Studies Chronic conditions Diabetes Exosomes Exosomes - metabolism Female Gene expression Genetic aspects Humans Kidney diseases Lupus Lupus Erythematosus, Systemic - urine Lupus nephritis Lupus Nephritis - metabolism Lupus Nephritis - urine Male MicroRNA MicroRNAs MicroRNAs - urine Middle Aged miRNA Nephritis Nutrition Obesity Patients Systemic lupus erythematosus Transfer RNA Ultracentrifugation Urine |
| title | Increased Urinary Exosomal MicroRNAs in Patients with Systemic Lupus Erythematosus |
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