title: Experimental diabetic nephropathy is accelerated in matrix metalloproteinase-2 knockout mice.
abstract: BACKGROUND
  Matrix metalloproteinase-2 (MMP-2) is responsible for the degradation of various types of extracellular matrix (ECM) proteins such as type IV collagen. Decreased MMP-2 expression and activity has been generally thought to contribute to increased accumulation of ECM at the advanced stage of diabetic nephropathy. However, the kinetics and role of MMP-2 in the early phase of diabetic nephropathy remain unclear. To address this issue, we examined whether streptozotocin (STZ)-induced early diabetic nephropathy was accelerated in MMP-2 knockout (KO) mice.
  
  
  METHODS
  Diabetes was induced by the injection of STZ in 6-week-old control and MMP-2 KO mice. Animals were killed after 16 weeks of diabetes of after observation alone.
  
  
  RESULTS
  Compared with non-diabetic control mice, renal MMP-2 expression and activity were increased in 16-week old diabetic mice. Serum levels of blood urea nitrogen and creatinine and urinary excretion levels of albumin and N-acetyl-β-D-glucosaminidase were significantly elevated in diabetic MMP-2 KO mice when compared with wild-type diabetic littermates. Further, accumulation of ECM in the glomeruli and atrophy and fibrosis in the tubulointerstitium were exacerbated, and renal α-smooth muscle actin expression was enhanced in diabetic MMP-2 KO mice.
  
  
  CONCLUSIONS
  Our present study suggests that renal expression and activity of MMP-2 are increased as a compensatory mechanism in the early phase of diabetic nephropathy. Since MMP-2 could play a protective role against the progression of diabetic nephropathy, further enhancement of MMP-2 expression and/or activity in the kidney may be a therapeutic target for the treatment of early diabetic nephropathy.
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takamiya
authors.forename: Kei
authors.initials: K
authors.lastname: Fukami
authors.forename: Sho-ichi
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kaida
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Nana
authors.initials: N
authors.lastname: Obara
authors.forename: Ryuji
authors.initials: R
authors.lastname: Iwatani
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Ando
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Koike
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nishino
authors.forename: Seiji
authors.initials: S
authors.lastname: Ueda
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
authors.forename: Seiya
authors.initials: S
authors.lastname: Okuda
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D003928:Diabetic Nephropathies / Q000201:enzymology*; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D020778:Matrix Metalloproteinase 2