title: Renoprotective action of a matrix metalloproteinase inhibitor in progressive mesangioproliferative nephritis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Shionogi and Co., Ltd., Toyonaka City, Japan.
authors: Takayuki
authors: T
authors: Kuroda
authors: Masao
authors: M
authors: Masui
authors: Mitsuru
authors: M
authors: Notoya
authors: Masashi
authors: M
authors: Ito
authors: Yoshinori
authors: Y
authors: Tamura
authors: Hiroyuki
authors: H
authors: Okamoto
authors: Eri
authors: E
authors: Kanaoka
authors: Toshihiro
authors: T
authors: Shinosaki