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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-1-9
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pubmed:abstractText |
Kidney injury molecule-1 (Kim-1) is associated with ischemic and proteinuric tubular injury; however, whether dysregulation of the renin-angiotensin system (RAS) can also induce Kim-1 is unknown. We studied Kim-1 expression in homozygous Ren2 rats, characterized by renal damage through excessive RAS activation. We also investigated whether antifibrotic treatment (RAS blockade or p38 MAP kinase inhibition) would affect Kim-1 expression. At 7 wk of age, homozygous Ren2 rats received a nonhypotensive dose of candesartan (0.05 mg x kg(-1) x day(-1) sc) or the p38 inhibitor SB-239063 (15 mg x kg(-1) x day(-1) sc) for 4 wk; untreated Ren2 and Sprague-Dawley (SD) rats served as controls. Kim-1 mRNA and protein expression were determined by quantitative PCR and immunohistochemistry, respectively, and related to markers of prefibrotic renal damage. Urinary Kim-1 was measured in 8-wk-old Ren2 and SD rats with and without angiotensin-converting enzyme inhibition (ramipril, 1 mg x kg(-1) x day(-1) in drinking water for 4 wk). Untreated Ren2 rats showed a >20-fold increase in renal Kim-1 mRNA (expressed as Kim-1-to-GAPDH ratio): 75.5 +/- 43.6 vs. 3.1 +/- 1.0 in SD rats (P < 0.01). Candesartan and SB-239063 strongly reduced Kim-1 mRNA: 3.1 +/- 1.5 (P < 0.01) and 9.8 +/- 4.2 (P < 0.05), respectively. Kim-1 protein expression in damaged tubules paralleled mRNA expression. Kim-1 expression correlated with renal osteopontin, alpha-smooth muscle actin, and collagen III expression and with tubulointerstitial fibrosis. Damaged tubular segments expressing activated p38 also expressed Kim-1. Urinary Kim-1 was increased in Ren2 vs. SD (458 +/- 70 vs. 27 +/- 2 pg/ml, P < 0.01) rats and abolished in Ren2 rats treated with ramipril (33 +/- 5 pg/ml, P < 0.01). Kim-1 is associated with development of RAS-mediated renal damage. Antifibrotic treatment through RAS blockade or p38 MAP kinase inhibition reduced Kim-1 in the homozygous Ren2 model.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aldosterone,
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II Type 1 Receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/Atrial Natriuretic Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Benzimidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Creatinine,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Havcr1protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Osteopontin,
http://linkedlifedata.com/resource/pubmed/chemical/Renin,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrazoles,
http://linkedlifedata.com/resource/pubmed/chemical/candesartan,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1931-857X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
292
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
F313-20
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pubmed:dateRevised |
2011-4-28
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pubmed:meshHeading |
pubmed-meshheading:16896183-Aldosterone,
pubmed-meshheading:16896183-Angiotensin II Type 1 Receptor Blockers,
pubmed-meshheading:16896183-Animals,
pubmed-meshheading:16896183-Animals, Genetically Modified,
pubmed-meshheading:16896183-Atrial Natriuretic Factor,
pubmed-meshheading:16896183-Benzimidazoles,
pubmed-meshheading:16896183-Biological Markers,
pubmed-meshheading:16896183-Blood Pressure,
pubmed-meshheading:16896183-Cell Adhesion Molecules,
pubmed-meshheading:16896183-Creatinine,
pubmed-meshheading:16896183-Enzyme Inhibitors,
pubmed-meshheading:16896183-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:16896183-Fibrosis,
pubmed-meshheading:16896183-Immunohistochemistry,
pubmed-meshheading:16896183-Male,
pubmed-meshheading:16896183-Membrane Proteins,
pubmed-meshheading:16896183-Nephritis, Interstitial,
pubmed-meshheading:16896183-Osteopontin,
pubmed-meshheading:16896183-Rats,
pubmed-meshheading:16896183-Rats, Inbred Strains,
pubmed-meshheading:16896183-Renin,
pubmed-meshheading:16896183-Renin-Angiotensin System,
pubmed-meshheading:16896183-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16896183-Tetrazoles,
pubmed-meshheading:16896183-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2007
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pubmed:articleTitle |
Induction of kidney injury molecule-1 in homozygous Ren2 rats is attenuated by blockade of the renin-angiotensin system or p38 MAP kinase.
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pubmed:affiliation |
Dept. of Pathology and Laboratory Medicine, Univ. Medical Center Groningen and Univ. of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands. m.h.de.borst@path.umcg.nl
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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