TY - JOUR
T1 - Tissue inhibitor of metalloproteinase-3 plays important roles in the kidney following unilateral ureteral obstruction
AU - Kawamoto, Hidenobu
AU - Yasuda, Osamu
AU - Suzuki, Takashi
AU - Ozaki, Tohru
AU - Yotsui, Takamori
AU - Higuchi, Masayoshi
AU - Rakugi, Hiromi
AU - Fukuo, Keisuke
AU - Ogihara, Toshio
AU - Maeda, Nobuyo
PY - 2006/4
Y1 - 2006/4
N2 - 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-β 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.
AB - 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-β 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.
KW - Extracellular matrix
KW - Hydronephrosis
KW - Matrix metalloproteinase
KW - Tissue inhibitor of metalloproteinase-3
KW - Unilateral ureteral obstruction
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U2 - 10.1291/hypres.29.285
DO - 10.1291/hypres.29.285
M3 - Article
C2 - 16778336
AN - SCOPUS:33744949958
SN - 0916-9636
VL - 29
SP - 285
EP - 294
JO - Hypertension Research
JF - Hypertension Research
IS - 4
ER -