Journal
HYPERTENSION RESEARCH
Volume 29, Issue 4, Pages 285-294Publisher
NATURE PUBLISHING GROUP
DOI: 10.1291/hypres.29.285
Keywords
extracellular matrix; matrix metalloproteinase; hydronephrosis; tissue inhibitor of metalloproteinase-3; unilateral ureteral obstruction
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Tissue inhibitor of metalloprotelnase-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 metalloprotelnase activities assessed by in situ zymography and transforming growth factor-ss 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.
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