Tubular kidney injury molecule-1 in protein-overload nephropathy
Kim-1, a recently discovered membrane protein, is undetectable in normal kidneys but markedly induced in proximal tubules after ischemic and toxic injury. The function of Kim-1 is unclear, but it is implicated in damage/repair processes. The Kim-1 ectodomain is cleaved by metalloproteinases and dete...
Gespeichert in:
| Veröffentlicht in: | American journal of physiology. Renal physiology 2006-08, Vol.291 (2), p.F456-F464 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | F464 |
|---|---|
| container_issue | 2 |
| container_start_page | F456 |
| container_title | American journal of physiology. Renal physiology |
| container_volume | 291 |
| creator | van Timmeren, Mirjan M Bakker, Stephan J L Vaidya, Vishal S Bailly, Veronique Schuurs, Theo A Damman, Jeffrey Stegeman, Coen A Bonventre, Joseph V van Goor, Harry |
| description | Kim-1, a recently discovered membrane protein, is undetectable in normal kidneys but markedly induced in proximal tubules after ischemic and toxic injury. The function of Kim-1 is unclear, but it is implicated in damage/repair processes. The Kim-1 ectodomain is cleaved by metalloproteinases and detectable in urine. We studied Kim-1 in a nontoxic, nonischemic, model of tubulointerstitial damage caused by acute proteinuria. Uninephrectomized (NX) rats received daily (ip) injections of 2 g BSA (NX+BSA, n = 12) or saline (NX, n = 6) for 3 wk. Kidneys were stained for various damage markers by immunohistochemistry (IHC). Kim-1 mRNA (RT-PCR, in situ hybridization), protein (IHC, Western blotting), and urinary Kim-1 (Luminex) were determined. Spatial relations between Kim-1 and other damage markers were studied by double labeling IHC. NX+BSA rats developed massive proteinuria (1,217 +/- 313 vs. 18 +/- 2 mg/day in NX, P < 0.001) and significant renal damage. Kim-1 mRNA was upregulated eightfold in NX+BSA (ratio Kim-1/beta-actin, 4.08 +/- 2.56 vs. 0.52 +/- 0.64 in NX, P < 0.001) and localized to damaged tubules. Kim-1 protein expression was markedly induced in NX+BSA (2.46 +/- 1.19 vs. 0.39 +/- 0.10% staining/field in NX, P < 0.001). Urinary Kim-1 was significantly elevated in NX+BSA (921 +/- 592 vs. 87 +/- 164 pg/ml in NX, P < 0.001) and correlated with tissue Kim-1 expression (r = 0.66, P =0.02). Kim-1 protein was found at the apical membrane of dilated nephrons. Kim-1 expression was limited to areas with inflammation (MØ), fibrosis (alpha-smooth muscle actin), and tubular damage (osteopontin), and only occasionally with tubular dedifferentiation (vimentin). These results implicate involvement of Kim-1 in the pathogenesis of proteinuria-induced renal damage/repair. Urinary Kim-1 levels may serve as a marker of proteinuria-induced renal damage. |
| doi_str_mv | 10.1152/ajprenal.00403.2005 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1152_ajprenal_00403_2005</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>16467126</sourcerecordid><originalsourceid>FETCH-LOGICAL-c459t-e8a649cae682f346c1808d449fb7ad265c6b136078e30c7625ec940abd4681a13</originalsourceid><addsrcrecordid>eNpFkN1Kw0AQhRdRbK0-gSB5gY0zu5vN5k4p_kHBmwrehc1mQhPzx6YR8vamtuLVHObwnYuPsVuEEDES97bqPbW2DgEUyFAARGdsOTeCo9L6fM6JRG6i-HPBroahAgBEgZdsgVrpGIVesoftmI219cFXmbc0BWVbjX4Kmq4mN9bEcf4Eve_2VLa8-yZfdzYPWup3vuvtfjdds4vC1gPdnO6KfTw_bdevfPP-8rZ-3HCnomTPyVitEmdJG1FIpR0aMLlSSZHFNhc6cjpDqSE2JMHFWkTkEgU2y5U2aFGumDzuOt8Ng6ci7X3ZWD-lCOnBR_rnI_31kR58zNTdkerHrKH8nzkJkD8UlF4t</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Tubular kidney injury molecule-1 in protein-overload nephropathy</title><source>MEDLINE</source><source>American Physiological Society</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>van Timmeren, Mirjan M ; Bakker, Stephan J L ; Vaidya, Vishal S ; Bailly, Veronique ; Schuurs, Theo A ; Damman, Jeffrey ; Stegeman, Coen A ; Bonventre, Joseph V ; van Goor, Harry</creator><creatorcontrib>van Timmeren, Mirjan M ; Bakker, Stephan J L ; Vaidya, Vishal S ; Bailly, Veronique ; Schuurs, Theo A ; Damman, Jeffrey ; Stegeman, Coen A ; Bonventre, Joseph V ; van Goor, Harry</creatorcontrib><description>Kim-1, a recently discovered membrane protein, is undetectable in normal kidneys but markedly induced in proximal tubules after ischemic and toxic injury. The function of Kim-1 is unclear, but it is implicated in damage/repair processes. The Kim-1 ectodomain is cleaved by metalloproteinases and detectable in urine. We studied Kim-1 in a nontoxic, nonischemic, model of tubulointerstitial damage caused by acute proteinuria. Uninephrectomized (NX) rats received daily (ip) injections of 2 g BSA (NX+BSA, n = 12) or saline (NX, n = 6) for 3 wk. Kidneys were stained for various damage markers by immunohistochemistry (IHC). Kim-1 mRNA (RT-PCR, in situ hybridization), protein (IHC, Western blotting), and urinary Kim-1 (Luminex) were determined. Spatial relations between Kim-1 and other damage markers were studied by double labeling IHC. NX+BSA rats developed massive proteinuria (1,217 +/- 313 vs. 18 +/- 2 mg/day in NX, P < 0.001) and significant renal damage. Kim-1 mRNA was upregulated eightfold in NX+BSA (ratio Kim-1/beta-actin, 4.08 +/- 2.56 vs. 0.52 +/- 0.64 in NX, P < 0.001) and localized to damaged tubules. Kim-1 protein expression was markedly induced in NX+BSA (2.46 +/- 1.19 vs. 0.39 +/- 0.10% staining/field in NX, P < 0.001). Urinary Kim-1 was significantly elevated in NX+BSA (921 +/- 592 vs. 87 +/- 164 pg/ml in NX, P < 0.001) and correlated with tissue Kim-1 expression (r = 0.66, P =0.02). Kim-1 protein was found at the apical membrane of dilated nephrons. Kim-1 expression was limited to areas with inflammation (MØ), fibrosis (alpha-smooth muscle actin), and tubular damage (osteopontin), and only occasionally with tubular dedifferentiation (vimentin). These results implicate involvement of Kim-1 in the pathogenesis of proteinuria-induced renal damage/repair. Urinary Kim-1 levels may serve as a marker of proteinuria-induced renal damage.</description><identifier>ISSN: 1931-857X</identifier><identifier>EISSN: 1522-1466</identifier><identifier>DOI: 10.1152/ajprenal.00403.2005</identifier><identifier>PMID: 16467126</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Blotting, Western ; Cell Adhesion Molecules - analysis ; Cell Adhesion Molecules - genetics ; Cell Adhesion Molecules - physiology ; Cell Adhesion Molecules - urine ; Gene Expression Regulation ; Immunohistochemistry ; Kidney Diseases - etiology ; Kidney Diseases - pathology ; Kidney Diseases - physiopathology ; Kidney Tubules - chemistry ; Kidney Tubules - pathology ; Kidney Tubules - physiopathology ; Male ; Membrane Proteins - analysis ; Membrane Proteins - genetics ; Membrane Proteins - physiology ; Membrane Proteins - urine ; Proteinuria - complications ; Proteinuria - physiopathology ; Rats ; Rats, Wistar ; RNA, Messenger - analysis ; RNA, Messenger - genetics ; Vimentin - analysis</subject><ispartof>American journal of physiology. Renal physiology, 2006-08, Vol.291 (2), p.F456-F464</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-e8a649cae682f346c1808d449fb7ad265c6b136078e30c7625ec940abd4681a13</citedby><cites>FETCH-LOGICAL-c459t-e8a649cae682f346c1808d449fb7ad265c6b136078e30c7625ec940abd4681a13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3026,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16467126$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van Timmeren, Mirjan M</creatorcontrib><creatorcontrib>Bakker, Stephan J L</creatorcontrib><creatorcontrib>Vaidya, Vishal S</creatorcontrib><creatorcontrib>Bailly, Veronique</creatorcontrib><creatorcontrib>Schuurs, Theo A</creatorcontrib><creatorcontrib>Damman, Jeffrey</creatorcontrib><creatorcontrib>Stegeman, Coen A</creatorcontrib><creatorcontrib>Bonventre, Joseph V</creatorcontrib><creatorcontrib>van Goor, Harry</creatorcontrib><title>Tubular kidney injury molecule-1 in protein-overload nephropathy</title><title>American journal of physiology. Renal physiology</title><addtitle>Am J Physiol Renal Physiol</addtitle><description>Kim-1, a recently discovered membrane protein, is undetectable in normal kidneys but markedly induced in proximal tubules after ischemic and toxic injury. The function of Kim-1 is unclear, but it is implicated in damage/repair processes. The Kim-1 ectodomain is cleaved by metalloproteinases and detectable in urine. We studied Kim-1 in a nontoxic, nonischemic, model of tubulointerstitial damage caused by acute proteinuria. Uninephrectomized (NX) rats received daily (ip) injections of 2 g BSA (NX+BSA, n = 12) or saline (NX, n = 6) for 3 wk. Kidneys were stained for various damage markers by immunohistochemistry (IHC). Kim-1 mRNA (RT-PCR, in situ hybridization), protein (IHC, Western blotting), and urinary Kim-1 (Luminex) were determined. Spatial relations between Kim-1 and other damage markers were studied by double labeling IHC. NX+BSA rats developed massive proteinuria (1,217 +/- 313 vs. 18 +/- 2 mg/day in NX, P < 0.001) and significant renal damage. Kim-1 mRNA was upregulated eightfold in NX+BSA (ratio Kim-1/beta-actin, 4.08 +/- 2.56 vs. 0.52 +/- 0.64 in NX, P < 0.001) and localized to damaged tubules. Kim-1 protein expression was markedly induced in NX+BSA (2.46 +/- 1.19 vs. 0.39 +/- 0.10% staining/field in NX, P < 0.001). Urinary Kim-1 was significantly elevated in NX+BSA (921 +/- 592 vs. 87 +/- 164 pg/ml in NX, P < 0.001) and correlated with tissue Kim-1 expression (r = 0.66, P =0.02). Kim-1 protein was found at the apical membrane of dilated nephrons. Kim-1 expression was limited to areas with inflammation (MØ), fibrosis (alpha-smooth muscle actin), and tubular damage (osteopontin), and only occasionally with tubular dedifferentiation (vimentin). These results implicate involvement of Kim-1 in the pathogenesis of proteinuria-induced renal damage/repair. Urinary Kim-1 levels may serve as a marker of proteinuria-induced renal damage.</description><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cell Adhesion Molecules - analysis</subject><subject>Cell Adhesion Molecules - genetics</subject><subject>Cell Adhesion Molecules - physiology</subject><subject>Cell Adhesion Molecules - urine</subject><subject>Gene Expression Regulation</subject><subject>Immunohistochemistry</subject><subject>Kidney Diseases - etiology</subject><subject>Kidney Diseases - pathology</subject><subject>Kidney Diseases - physiopathology</subject><subject>Kidney Tubules - chemistry</subject><subject>Kidney Tubules - pathology</subject><subject>Kidney Tubules - physiopathology</subject><subject>Male</subject><subject>Membrane Proteins - analysis</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - physiology</subject><subject>Membrane Proteins - urine</subject><subject>Proteinuria - complications</subject><subject>Proteinuria - physiopathology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>RNA, Messenger - analysis</subject><subject>RNA, Messenger - genetics</subject><subject>Vimentin - analysis</subject><issn>1931-857X</issn><issn>1522-1466</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkN1Kw0AQhRdRbK0-gSB5gY0zu5vN5k4p_kHBmwrehc1mQhPzx6YR8vamtuLVHObwnYuPsVuEEDES97bqPbW2DgEUyFAARGdsOTeCo9L6fM6JRG6i-HPBroahAgBEgZdsgVrpGIVesoftmI219cFXmbc0BWVbjX4Kmq4mN9bEcf4Eve_2VLa8-yZfdzYPWup3vuvtfjdds4vC1gPdnO6KfTw_bdevfPP-8rZ-3HCnomTPyVitEmdJG1FIpR0aMLlSSZHFNhc6cjpDqSE2JMHFWkTkEgU2y5U2aFGumDzuOt8Ng6ci7X3ZWD-lCOnBR_rnI_31kR58zNTdkerHrKH8nzkJkD8UlF4t</recordid><startdate>20060801</startdate><enddate>20060801</enddate><creator>van Timmeren, Mirjan M</creator><creator>Bakker, Stephan J L</creator><creator>Vaidya, Vishal S</creator><creator>Bailly, Veronique</creator><creator>Schuurs, Theo A</creator><creator>Damman, Jeffrey</creator><creator>Stegeman, Coen A</creator><creator>Bonventre, Joseph V</creator><creator>van Goor, Harry</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20060801</creationdate><title>Tubular kidney injury molecule-1 in protein-overload nephropathy</title><author>van Timmeren, Mirjan M ; Bakker, Stephan J L ; Vaidya, Vishal S ; Bailly, Veronique ; Schuurs, Theo A ; Damman, Jeffrey ; Stegeman, Coen A ; Bonventre, Joseph V ; van Goor, Harry</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-e8a649cae682f346c1808d449fb7ad265c6b136078e30c7625ec940abd4681a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cell Adhesion Molecules - analysis</topic><topic>Cell Adhesion Molecules - genetics</topic><topic>Cell Adhesion Molecules - physiology</topic><topic>Cell Adhesion Molecules - urine</topic><topic>Gene Expression Regulation</topic><topic>Immunohistochemistry</topic><topic>Kidney Diseases - etiology</topic><topic>Kidney Diseases - pathology</topic><topic>Kidney Diseases - physiopathology</topic><topic>Kidney Tubules - chemistry</topic><topic>Kidney Tubules - pathology</topic><topic>Kidney Tubules - physiopathology</topic><topic>Male</topic><topic>Membrane Proteins - analysis</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - physiology</topic><topic>Membrane Proteins - urine</topic><topic>Proteinuria - complications</topic><topic>Proteinuria - physiopathology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>RNA, Messenger - analysis</topic><topic>RNA, Messenger - genetics</topic><topic>Vimentin - analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van Timmeren, Mirjan M</creatorcontrib><creatorcontrib>Bakker, Stephan J L</creatorcontrib><creatorcontrib>Vaidya, Vishal S</creatorcontrib><creatorcontrib>Bailly, Veronique</creatorcontrib><creatorcontrib>Schuurs, Theo A</creatorcontrib><creatorcontrib>Damman, Jeffrey</creatorcontrib><creatorcontrib>Stegeman, Coen A</creatorcontrib><creatorcontrib>Bonventre, Joseph V</creatorcontrib><creatorcontrib>van Goor, Harry</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>American journal of physiology. Renal physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van Timmeren, Mirjan M</au><au>Bakker, Stephan J L</au><au>Vaidya, Vishal S</au><au>Bailly, Veronique</au><au>Schuurs, Theo A</au><au>Damman, Jeffrey</au><au>Stegeman, Coen A</au><au>Bonventre, Joseph V</au><au>van Goor, Harry</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tubular kidney injury molecule-1 in protein-overload nephropathy</atitle><jtitle>American journal of physiology. Renal physiology</jtitle><addtitle>Am J Physiol Renal Physiol</addtitle><date>2006-08-01</date><risdate>2006</risdate><volume>291</volume><issue>2</issue><spage>F456</spage><epage>F464</epage><pages>F456-F464</pages><issn>1931-857X</issn><eissn>1522-1466</eissn><abstract>Kim-1, a recently discovered membrane protein, is undetectable in normal kidneys but markedly induced in proximal tubules after ischemic and toxic injury. The function of Kim-1 is unclear, but it is implicated in damage/repair processes. The Kim-1 ectodomain is cleaved by metalloproteinases and detectable in urine. We studied Kim-1 in a nontoxic, nonischemic, model of tubulointerstitial damage caused by acute proteinuria. Uninephrectomized (NX) rats received daily (ip) injections of 2 g BSA (NX+BSA, n = 12) or saline (NX, n = 6) for 3 wk. Kidneys were stained for various damage markers by immunohistochemistry (IHC). Kim-1 mRNA (RT-PCR, in situ hybridization), protein (IHC, Western blotting), and urinary Kim-1 (Luminex) were determined. Spatial relations between Kim-1 and other damage markers were studied by double labeling IHC. NX+BSA rats developed massive proteinuria (1,217 +/- 313 vs. 18 +/- 2 mg/day in NX, P < 0.001) and significant renal damage. Kim-1 mRNA was upregulated eightfold in NX+BSA (ratio Kim-1/beta-actin, 4.08 +/- 2.56 vs. 0.52 +/- 0.64 in NX, P < 0.001) and localized to damaged tubules. Kim-1 protein expression was markedly induced in NX+BSA (2.46 +/- 1.19 vs. 0.39 +/- 0.10% staining/field in NX, P < 0.001). Urinary Kim-1 was significantly elevated in NX+BSA (921 +/- 592 vs. 87 +/- 164 pg/ml in NX, P < 0.001) and correlated with tissue Kim-1 expression (r = 0.66, P =0.02). Kim-1 protein was found at the apical membrane of dilated nephrons. Kim-1 expression was limited to areas with inflammation (MØ), fibrosis (alpha-smooth muscle actin), and tubular damage (osteopontin), and only occasionally with tubular dedifferentiation (vimentin). These results implicate involvement of Kim-1 in the pathogenesis of proteinuria-induced renal damage/repair. Urinary Kim-1 levels may serve as a marker of proteinuria-induced renal damage.</abstract><cop>United States</cop><pmid>16467126</pmid><doi>10.1152/ajprenal.00403.2005</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1931-857X |
| ispartof | American journal of physiology. Renal physiology, 2006-08, Vol.291 (2), p.F456-F464 |
| issn | 1931-857X 1522-1466 |
| language | eng |
| recordid | cdi_crossref_primary_10_1152_ajprenal_00403_2005 |
| source | MEDLINE; American Physiological Society; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Blotting, Western Cell Adhesion Molecules - analysis Cell Adhesion Molecules - genetics Cell Adhesion Molecules - physiology Cell Adhesion Molecules - urine Gene Expression Regulation Immunohistochemistry Kidney Diseases - etiology Kidney Diseases - pathology Kidney Diseases - physiopathology Kidney Tubules - chemistry Kidney Tubules - pathology Kidney Tubules - physiopathology Male Membrane Proteins - analysis Membrane Proteins - genetics Membrane Proteins - physiology Membrane Proteins - urine Proteinuria - complications Proteinuria - physiopathology Rats Rats, Wistar RNA, Messenger - analysis RNA, Messenger - genetics Vimentin - analysis |
| title | Tubular kidney injury molecule-1 in protein-overload nephropathy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T17%3A07%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Tubular%20kidney%20injury%20molecule-1%20in%20protein-overload%20nephropathy&rft.jtitle=American%20journal%20of%20physiology.%20Renal%20physiology&rft.au=van%20Timmeren,%20Mirjan%20M&rft.date=2006-08-01&rft.volume=291&rft.issue=2&rft.spage=F456&rft.epage=F464&rft.pages=F456-F464&rft.issn=1931-857X&rft.eissn=1522-1466&rft_id=info:doi/10.1152/ajprenal.00403.2005&rft_dat=%3Cpubmed_cross%3E16467126%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/16467126&rfr_iscdi=true |