title: Tissue inhibitor of metalloproteinase-3 plays important roles in the kidney following unilateral ureteral obstruction.
abstract: 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.
authors.affiliation: Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Kawamoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Yasuda
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tohru
authors.initials: T
authors.lastname: Ozaki
authors.forename: Takamori
authors.initials: T
authors.lastname: Yotsui
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Higuchi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Fukuo
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
mesh_terms: D000818:Animals; D001794:Blood Pressure; D005109:Extracellular Matrix / Q000201:enzymology / Q000473:pathology; D006339:Heart Rate; D006869:Hydronephrosis / Q000473:pathology / Q000503:physiopathology; D007672:Kidney Cortex / Q000473:pathology / Q000503:physiopathology; D007679:Kidney Medulla / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics* / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014517:Ureteral Obstruction / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D019717:Tissue Inhibitor of Metalloproteinase-3; D016212:Transforming Growth Factor beta