Quantitative and qualitative urinary cellular patterns correlate with progression of murine glomerulonephritis
The kidney is a nonregenerative organ composed of numerous functional nephrons and collecting ducts (CDs). Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been repo...
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description | The kidney is a nonregenerative organ composed of numerous functional nephrons and collecting ducts (CDs). Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology.Urinary cytology and renal histopathology were analyzed in BXSB/MpJ (BXSB; glomerulonephritis model) and C57BL/6 (B6; control) mice. Urinary cytology revealed that the number of urinary cells in BXSB mice changed according to the histometric score of glomerulonephritis and urinary albumin; however, no correlation was detected for the levels of blood urea nitrogen and creatinine. The expression of specific markers for podocytes, distal tubules (DTs), and CDs was detected in BXSB urine. Cells immunopositive for Wilms tumor 1 (podocyte marker) and interleukin-1 family, member 6 (damaged DT and CD marker) in the kidney significantly decreased and increased in BXSB versus B6, respectively. In the PCR array analysis of inflammatory cytokines and chemokines, Il10, Cxcl2, C3, and Il1rn showed relatively higher expression in BXSB kidneys than in B6 kidneys. In particular, the highest expression of C3 mRNA was detected in the urine from BXSB mice. Furthermore, C3 protein and mRNA were localized in the epithelia of damaged nephrons.These findings suggest that epithelial cells of the glomerulus, DT, and CD are dropped into the urine, and that these patterns are associated with renal pathology progression. We conclude that evaluation of urinary cellular patterns plays a key role in the early, noninvasive diagnosis of renal disease. |
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Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology.Urinary cytology and renal histopathology were analyzed in BXSB/MpJ (BXSB; glomerulonephritis model) and C57BL/6 (B6; control) mice. Urinary cytology revealed that the number of urinary cells in BXSB mice changed according to the histometric score of glomerulonephritis and urinary albumin; however, no correlation was detected for the levels of blood urea nitrogen and creatinine. The expression of specific markers for podocytes, distal tubules (DTs), and CDs was detected in BXSB urine. Cells immunopositive for Wilms tumor 1 (podocyte marker) and interleukin-1 family, member 6 (damaged DT and CD marker) in the kidney significantly decreased and increased in BXSB versus B6, respectively. In the PCR array analysis of inflammatory cytokines and chemokines, Il10, Cxcl2, C3, and Il1rn showed relatively higher expression in BXSB kidneys than in B6 kidneys. In particular, the highest expression of C3 mRNA was detected in the urine from BXSB mice. Furthermore, C3 protein and mRNA were localized in the epithelia of damaged nephrons.These findings suggest that epithelial cells of the glomerulus, DT, and CD are dropped into the urine, and that these patterns are associated with renal pathology progression. We conclude that evaluation of urinary cellular patterns plays a key role in the early, noninvasive diagnosis of renal disease.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0016472</identifier><identifier>PMID: 21304992</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Albumin ; Analysis ; Animals ; Autoimmune diseases ; Biomarkers - urine ; Biosynthesis ; C3 protein ; Cell Count ; Chemokines ; Correlation ; Creatinine ; Cytokines ; Cytology ; Damage localization ; Distal tubules ; Epithelial cells ; Epithelial Cells - pathology ; Fibroblasts ; Gene expression ; Glomerulonephritis ; Glomerulonephritis - diagnosis ; Glomerulonephritis - urine ; Glomerulus ; Histochemistry ; Histopathology ; House mouse ; Inflammation ; Inflammatory diseases ; Interleukin 1 ; Interleukin 10 ; Kidney diseases ; Kidney Diseases - diagnosis ; Kidney Tubules, Distal - pathology ; Kidneys ; Laboratory animals ; Medicine ; Mice ; Mice, Inbred C57BL ; mRNA ; Nephrons ; Pathology ; Physiological aspects ; Podocytes - pathology ; Proteins ; Qualitative analysis ; Renal function ; RNA ; Rodents ; Urea ; Urine ; Urine - cytology ; Veterinary colleges ; Veterinary medicine ; WT1 protein</subject><ispartof>PloS one, 2011-01, Vol.6 (1), p.e16472-e16472</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Kimura et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>Kimura et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c735t-2c1058b8547b15841f71005637b9a0c204736889ba0e3b18502a2fcb941eaad53</citedby><cites>FETCH-LOGICAL-c735t-2c1058b8547b15841f71005637b9a0c204736889ba0e3b18502a2fcb941eaad53</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/PMC3031591/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031591/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21304992$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Brown, Justin</contributor><creatorcontrib>Kimura, Junpei</creatorcontrib><creatorcontrib>Ichii, Osamu</creatorcontrib><creatorcontrib>Otsuka, Saori</creatorcontrib><creatorcontrib>Kanazawa, Tomonori</creatorcontrib><creatorcontrib>Namiki, Yuka</creatorcontrib><creatorcontrib>Hashimoto, Yoshiharu</creatorcontrib><creatorcontrib>Kon, Yasuhiro</creatorcontrib><title>Quantitative and qualitative urinary cellular patterns correlate with progression of murine glomerulonephritis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The kidney is a nonregenerative organ composed of numerous functional nephrons and collecting ducts (CDs). Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology.Urinary cytology and renal histopathology were analyzed in BXSB/MpJ (BXSB; glomerulonephritis model) and C57BL/6 (B6; control) mice. Urinary cytology revealed that the number of urinary cells in BXSB mice changed according to the histometric score of glomerulonephritis and urinary albumin; however, no correlation was detected for the levels of blood urea nitrogen and creatinine. The expression of specific markers for podocytes, distal tubules (DTs), and CDs was detected in BXSB urine. Cells immunopositive for Wilms tumor 1 (podocyte marker) and interleukin-1 family, member 6 (damaged DT and CD marker) in the kidney significantly decreased and increased in BXSB versus B6, respectively. In the PCR array analysis of inflammatory cytokines and chemokines, Il10, Cxcl2, C3, and Il1rn showed relatively higher expression in BXSB kidneys than in B6 kidneys. In particular, the highest expression of C3 mRNA was detected in the urine from BXSB mice. Furthermore, C3 protein and mRNA were localized in the epithelia of damaged nephrons.These findings suggest that epithelial cells of the glomerulus, DT, and CD are dropped into the urine, and that these patterns are associated with renal pathology progression. We conclude that evaluation of urinary cellular patterns plays a key role in the early, noninvasive diagnosis of renal disease.</description><subject>Albumin</subject><subject>Analysis</subject><subject>Animals</subject><subject>Autoimmune diseases</subject><subject>Biomarkers - urine</subject><subject>Biosynthesis</subject><subject>C3 protein</subject><subject>Cell Count</subject><subject>Chemokines</subject><subject>Correlation</subject><subject>Creatinine</subject><subject>Cytokines</subject><subject>Cytology</subject><subject>Damage localization</subject><subject>Distal tubules</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - pathology</subject><subject>Fibroblasts</subject><subject>Gene expression</subject><subject>Glomerulonephritis</subject><subject>Glomerulonephritis - diagnosis</subject><subject>Glomerulonephritis - urine</subject><subject>Glomerulus</subject><subject>Histochemistry</subject><subject>Histopathology</subject><subject>House mouse</subject><subject>Inflammation</subject><subject>Inflammatory diseases</subject><subject>Interleukin 1</subject><subject>Interleukin 10</subject><subject>Kidney diseases</subject><subject>Kidney Diseases - diagnosis</subject><subject>Kidney Tubules, Distal - pathology</subject><subject>Kidneys</subject><subject>Laboratory animals</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>mRNA</subject><subject>Nephrons</subject><subject>Pathology</subject><subject>Physiological aspects</subject><subject>Podocytes - pathology</subject><subject>Proteins</subject><subject>Qualitative analysis</subject><subject>Renal function</subject><subject>RNA</subject><subject>Rodents</subject><subject>Urea</subject><subject>Urine</subject><subject>Urine - cytology</subject><subject>Veterinary colleges</subject><subject>Veterinary medicine</subject><subject>WT1 protein</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</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>eNqNk1uL1DAUx4so7rr6DUQLguLDjLn1kpeFZfEysLB4fQ1petrJkEm6SbrqtzfjdJap7IPkoWny-__PyUlOlj3HaIlphd9t3OitNMvBWVgihEtWkQfZKeaULEqC6MOj-Un2JIQNQgWty_JxdkIwRYxzcprZz6O0UUcZ9S3k0rb5zSjN4X_02kr_O1dgzGikzwcZI3gbcuW8ByMj5D91XOeDd72HELSzuevy7U4IeW_cFvxoUobD2uuow9PsUSdNgGfT9yz7_uH9t8tPi6vrj6vLi6uFqmgRF0RhVNRNXbCqwUXNcFfhlH1Jq4ZLpAhiFS3rmjcSAW1wXSAiSacazjBI2Rb0LHu59x2MC2IqVRCYJILzCpeJWO2J1smNGLzepoMKJ7X4u-B8L6SPWhkQHanrFrqSYVywFJOrluICYV63GABY8jqfoo3NFloFNnppZqbzHavXone3gqJkxHEyeDMZeHczQohiq8Ou6NKCG4OoC0xIhQhJ5Kt_yPsPN1G9TPlr27kUVu08xQWrSo7KkqFELe-h0mhhq1W6tE6n9Zng7UyQmAi_Yi_HEMTq65f_Z69_zNnXR-wapInr4MwY03MKc5DtQeVdCB66uxpjJHZdcaiG2HWFmLoiyV4c38-d6NAG9A9wiwkz</recordid><startdate>20110131</startdate><enddate>20110131</enddate><creator>Kimura, Junpei</creator><creator>Ichii, Osamu</creator><creator>Otsuka, Saori</creator><creator>Kanazawa, Tomonori</creator><creator>Namiki, Yuka</creator><creator>Hashimoto, Yoshiharu</creator><creator>Kon, Yasuhiro</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>20110131</creationdate><title>Quantitative and qualitative urinary cellular patterns correlate with progression of murine glomerulonephritis</title><author>Kimura, Junpei ; Ichii, Osamu ; Otsuka, Saori ; Kanazawa, Tomonori ; Namiki, Yuka ; Hashimoto, Yoshiharu ; Kon, Yasuhiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c735t-2c1058b8547b15841f71005637b9a0c204736889ba0e3b18502a2fcb941eaad53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Albumin</topic><topic>Analysis</topic><topic>Animals</topic><topic>Autoimmune diseases</topic><topic>Biomarkers - urine</topic><topic>Biosynthesis</topic><topic>C3 protein</topic><topic>Cell Count</topic><topic>Chemokines</topic><topic>Correlation</topic><topic>Creatinine</topic><topic>Cytokines</topic><topic>Cytology</topic><topic>Damage localization</topic><topic>Distal tubules</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - pathology</topic><topic>Fibroblasts</topic><topic>Gene expression</topic><topic>Glomerulonephritis</topic><topic>Glomerulonephritis - diagnosis</topic><topic>Glomerulonephritis - urine</topic><topic>Glomerulus</topic><topic>Histochemistry</topic><topic>Histopathology</topic><topic>House mouse</topic><topic>Inflammation</topic><topic>Inflammatory diseases</topic><topic>Interleukin 1</topic><topic>Interleukin 10</topic><topic>Kidney diseases</topic><topic>Kidney Diseases - diagnosis</topic><topic>Kidney Tubules, Distal - pathology</topic><topic>Kidneys</topic><topic>Laboratory animals</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>mRNA</topic><topic>Nephrons</topic><topic>Pathology</topic><topic>Physiological aspects</topic><topic>Podocytes - 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Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology.Urinary cytology and renal histopathology were analyzed in BXSB/MpJ (BXSB; glomerulonephritis model) and C57BL/6 (B6; control) mice. Urinary cytology revealed that the number of urinary cells in BXSB mice changed according to the histometric score of glomerulonephritis and urinary albumin; however, no correlation was detected for the levels of blood urea nitrogen and creatinine. The expression of specific markers for podocytes, distal tubules (DTs), and CDs was detected in BXSB urine. Cells immunopositive for Wilms tumor 1 (podocyte marker) and interleukin-1 family, member 6 (damaged DT and CD marker) in the kidney significantly decreased and increased in BXSB versus B6, respectively. In the PCR array analysis of inflammatory cytokines and chemokines, Il10, Cxcl2, C3, and Il1rn showed relatively higher expression in BXSB kidneys than in B6 kidneys. In particular, the highest expression of C3 mRNA was detected in the urine from BXSB mice. Furthermore, C3 protein and mRNA were localized in the epithelia of damaged nephrons.These findings suggest that epithelial cells of the glomerulus, DT, and CD are dropped into the urine, and that these patterns are associated with renal pathology progression. We conclude that evaluation of urinary cellular patterns plays a key role in the early, noninvasive diagnosis of renal disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21304992</pmid><doi>10.1371/journal.pone.0016472</doi><tpages>e16472</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Albumin Analysis Animals Autoimmune diseases Biomarkers - urine Biosynthesis C3 protein Cell Count Chemokines Correlation Creatinine Cytokines Cytology Damage localization Distal tubules Epithelial cells Epithelial Cells - pathology Fibroblasts Gene expression Glomerulonephritis Glomerulonephritis - diagnosis Glomerulonephritis - urine Glomerulus Histochemistry Histopathology House mouse Inflammation Inflammatory diseases Interleukin 1 Interleukin 10 Kidney diseases Kidney Diseases - diagnosis Kidney Tubules, Distal - pathology Kidneys Laboratory animals Medicine Mice Mice, Inbred C57BL mRNA Nephrons Pathology Physiological aspects Podocytes - pathology Proteins Qualitative analysis Renal function RNA Rodents Urea Urine Urine - cytology Veterinary colleges Veterinary medicine WT1 protein |
title | Quantitative and qualitative urinary cellular patterns correlate with progression of murine glomerulonephritis |
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