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 RIS Download
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