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Tissue inhibitor of metalloproteinase-3 plays important roles in the kidney following unilateral ureteral obstruction.

Tissue inhibitor of metalloproteinase-3 (Timp-3), an inhibitor of matrix-degrading enzymes, is an important molecule for maintenance of the extracellular matrix. In this study, we generated Timp-3-deficient mice and used them to examine the effect of Timp-3-deficiency on blood pressure and to investigate the role of Timp-3 in the kidney following unilateral ureteral obstruction. The blood pressure and heart rate of Timp-3-deficient mice were not significantly different from those of wild-type mice. On the other hand, the obstructed kidneys of Timp-3-deficient mice developed more severe hydronephrosis than those of wild-type animals. Matrix metalloproteinase activities assessed by in situ zymography and transforming growth factor-beta expression were elevated in Timp-3-deficient mice. The renal tissues were thinner and the ratio of renal medulla to cortex was significantly lower in the obstructed Timp-3-deficient kidneys. These findings indicate that Timp-3-deficiency does not substantially affect the blood pressure in mice, and that Timp-3 plays an important role in the maintenance of renal macrostructure after unilateral ureteral obstruction.

Pubmed ID: 16778336


  • Kawamoto H
  • Yasuda O
  • Suzuki T
  • Ozaki T
  • Yotsui T
  • Higuchi M
  • Rakugi H
  • Fukuo K
  • Ogihara T
  • Maeda N


Hypertension research : official journal of the Japanese Society of Hypertension

Publication Data

April 16, 2006

Associated Grants


Mesh Terms

  • Animals
  • Blood Pressure
  • Extracellular Matrix
  • Heart Rate
  • Hydronephrosis
  • Kidney Cortex
  • Kidney Medulla
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Tissue Inhibitor of Metalloproteinase-3
  • Transforming Growth Factor beta
  • Ureteral Obstruction