Journal Article

Experimental diabetic nephropathy is accelerated in matrix metalloproteinase-2 knockout mice

Yoshimi Takamiya, Kei Fukami, Sho-ichi Yamagishi, Yusuke Kaida, Yosuke Nakayama, Nana Obara, Ryuji Iwatani, Ryotaro Ando, Kiyomi Koike, Takanori Matsui, Yuri Nishino, Seiji Ueda, Mark E. Cooper and Seiya Okuda

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 28, issue 1, pages 55-62
Published in print January 2013 | ISSN: 0931-0509
Published online September 2012 | e-ISSN: 1460-2385 | DOI:
Experimental diabetic nephropathy is accelerated in matrix metalloproteinase-2 knockout mice

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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.


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.


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.


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.

Keywords: albuminuria; diabetic nephropathy; extracellular matrix; MMP-2; tubulointerstitial injury

Journal Article.  3785 words.  Illustrated.

Subjects: Nephrology

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