Renoprotective Action of a Matrix Metalloproteinase Inhibitor in Progressive Mesangioproliferative Nephritis
Background/Aim: Matrix metalloproteinases (MMPs) play pivotal roles in extracellular matrix turnover and are involved in chronic kidney disease. The renoprotective action of a synthetic MMP inhibitor, compound A, was investigated in chronic nephritis. Methods: Nephritis was induced by a single injec...
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doaj-b6575dd8de12430aafacfb65848c304c2020-11-25T00:24:02ZengKarger PublishersNephron Extra1664-55292012-05-012113314610.1159/000338801338801Renoprotective Action of a Matrix Metalloproteinase Inhibitor in Progressive Mesangioproliferative NephritisTakayuki KurodaMasao MasuiMitsuru NotoyaMasashi ItoYoshinori TamuraHiroyuki OkamotoEri KanaokaToshihiro ShinosakiBackground/Aim: Matrix metalloproteinases (MMPs) play pivotal roles in extracellular matrix turnover and are involved in chronic kidney disease. The renoprotective action of a synthetic MMP inhibitor, compound A, was investigated in chronic nephritis. Methods: Nephritis was induced by a single injection of anti-Thy1.1 antibody to unilaterally nephrectomized rats. The effects of compound A on proteinuria, blood urea nitrogen, and matrix-related gene expressions were evaluated. Collagen accumulation, as assessed by periodic acid-Schiff staining and hydroxyproline content, was determined. The integrity of glomerular epithelial cells and glomerular basement membrane was evaluated with desmin immunohistochemistry and electron microscopic detection of anionic charge sites, respectively. Results: Treatment with compound A notably attenuated proteinuria, ameliorated blood urea nitrogen, and prevented glomerulosclerosis. Gene upregulation of collagen and transforming growth factor β1 in the cortex was prevented in the treated animals. Glomerular epithelial cell injury was milder, and glomerular basement membrane anionic sites were protected with the treatment. Conclusion: A novel MMP inhibitor, compound A, exerts protective effects in progressive glomerulonephritis. Compound A ameliorates various aspects of renal injuries and may have therapeutic potential toward kidney diseases.http://www.karger.com/Article/FullText/338801Matrix metalloproteinase-2GlomerulonephritisGlomerular basement membraneGlomerular epithelial cellsExtracellular matrix |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Takayuki Kuroda Masao Masui Mitsuru Notoya Masashi Ito Yoshinori Tamura Hiroyuki Okamoto Eri Kanaoka Toshihiro Shinosaki |
spellingShingle |
Takayuki Kuroda Masao Masui Mitsuru Notoya Masashi Ito Yoshinori Tamura Hiroyuki Okamoto Eri Kanaoka Toshihiro Shinosaki Renoprotective Action of a Matrix Metalloproteinase Inhibitor in Progressive Mesangioproliferative Nephritis Nephron Extra Matrix metalloproteinase-2 Glomerulonephritis Glomerular basement membrane Glomerular epithelial cells Extracellular matrix |
author_facet |
Takayuki Kuroda Masao Masui Mitsuru Notoya Masashi Ito Yoshinori Tamura Hiroyuki Okamoto Eri Kanaoka Toshihiro Shinosaki |
author_sort |
Takayuki Kuroda |
title |
Renoprotective Action of a Matrix Metalloproteinase Inhibitor in Progressive Mesangioproliferative Nephritis |
title_short |
Renoprotective Action of a Matrix Metalloproteinase Inhibitor in Progressive Mesangioproliferative Nephritis |
title_full |
Renoprotective Action of a Matrix Metalloproteinase Inhibitor in Progressive Mesangioproliferative Nephritis |
title_fullStr |
Renoprotective Action of a Matrix Metalloproteinase Inhibitor in Progressive Mesangioproliferative Nephritis |
title_full_unstemmed |
Renoprotective Action of a Matrix Metalloproteinase Inhibitor in Progressive Mesangioproliferative Nephritis |
title_sort |
renoprotective action of a matrix metalloproteinase inhibitor in progressive mesangioproliferative nephritis |
publisher |
Karger Publishers |
series |
Nephron Extra |
issn |
1664-5529 |
publishDate |
2012-05-01 |
description |
Background/Aim: Matrix metalloproteinases (MMPs) play pivotal roles in extracellular matrix turnover and are involved in chronic kidney disease. The renoprotective action of a synthetic MMP inhibitor, compound A, was investigated in chronic nephritis. Methods: Nephritis was induced by a single injection of anti-Thy1.1 antibody to unilaterally nephrectomized rats. The effects of compound A on proteinuria, blood urea nitrogen, and matrix-related gene expressions were evaluated. Collagen accumulation, as assessed by periodic acid-Schiff staining and hydroxyproline content, was determined. The integrity of glomerular epithelial cells and glomerular basement membrane was evaluated with desmin immunohistochemistry and electron microscopic detection of anionic charge sites, respectively. Results: Treatment with compound A notably attenuated proteinuria, ameliorated blood urea nitrogen, and prevented glomerulosclerosis. Gene upregulation of collagen and transforming growth factor β1 in the cortex was prevented in the treated animals. Glomerular epithelial cell injury was milder, and glomerular basement membrane anionic sites were protected with the treatment. Conclusion: A novel MMP inhibitor, compound A, exerts protective effects in progressive glomerulonephritis. Compound A ameliorates various aspects of renal injuries and may have therapeutic potential toward kidney diseases. |
topic |
Matrix metalloproteinase-2 Glomerulonephritis Glomerular basement membrane Glomerular epithelial cells Extracellular matrix |
url |
http://www.karger.com/Article/FullText/338801 |
work_keys_str_mv |
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