論文 - 詳細
| RRC ID | 18534 |
|---|---|
| 著者 | Takamiya Y, Fukami K, Yamagishi S, Kaida Y, Nakayama Y, Obara N, Iwatani R, Ando R, Koike K, Matsui T, Nishino Y, Ueda S, Cooper ME, Okuda S. |
| タイトル | Experimental diabetic nephropathy is accelerated in matrix metalloproteinase-2 knockout mice. |
| ジャーナル | Nephrol Dial Transplant |
| 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. |
| 巻・号 | 28(1) |
| ページ | 55-62 |
| 公開日 | 2013-1-1 |
| DOI | 10.1093/ndt/gfs387 |
| PII | gfs387 |
| PMID | 23028104 |
| MeSH | Animals Blotting, Western Diabetes Mellitus, Experimental / enzymology* Diabetic Nephropathies / enzymology* Immunohistochemistry Kidney / pathology* Kidney / physiopathology Kidney Function Tests Male Matrix Metalloproteinase 2 / genetics Matrix Metalloproteinase 2 / metabolism* Mice Mice, Knockout Real-Time Polymerase Chain Reaction |
| IF | 4.531 |
| 引用数 | 37 |
| WOS 分野 | UROLOGY & NEPHROLOGY TRANSPLANTATION |
| リソース情報 | |
| 実験動物マウス | RBRC00398 |