Abstract | BACKGROUND: METHODS: Adolescent male dogs that developed renal failure were euthanized and necropsied. Clinicopathologic features of the disease were characterized, and kidneys from normal and Alport dogs were analyzed by gelatin zymography, Western blotting, in situ zymography, immunohistology, and by reverse transcription polymerase chain reaction (RT-PCR) for expression of MMP-2, MMP-9, and membrane type 1-MMP (MT1-MMP). RESULTS: Affected dogs developed proteinuria and rapidly progressive juvenile-onset chronic renal failure. The activities of MMP-2 and MMP-9 were significantly induced in Alport kidney. In situ zymography confirmed elevated active metalloproteinases in kidney cryosections of affected dogs. The mRNAs encoding MMP-2, MMP-9 and MT1-MMP were also increased in Alport dogs suggesting that elevated expression of MMPs reflects events in the progression of Alport syndrome in dogs. CONCLUSION: Elevated expression of MMP-2, MMP-9, and MT1-MMP is observed in fibrotic renal cortex from X-linked Alport syndrome dogs. These findings suggest that MMPs may play an important role in matrix accumulation associated with progressive renal scarring in this model.
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Authors | Velidi H Rao, George E Lees, Clifford E Kashtan, Ryochi Nemori, Rakesh K Singh, Daniel T Meehan, Kathyrn Rodgers, Brian R Berridge, Gautam Bhattacharya, Dominic Cosgrove |
Journal | Kidney international
(Kidney Int)
Vol. 63
Issue 5
Pg. 1736-48
(May 2003)
ISSN: 0085-2538 [Print] United States |
PMID | 12675849
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- RNA, Messenger
- Gelatin
- Matrix Metalloproteinases, Membrane-Associated
- Metalloendopeptidases
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
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Topics |
- Animals
- Dogs
- Fibrosis
- Gelatin
- Gene Expression Regulation, Enzymologic
- Kidney Cortex
(enzymology, pathology)
- Matrix Metalloproteinase 2
(genetics, metabolism)
- Matrix Metalloproteinase 9
(genetics, metabolism)
- Matrix Metalloproteinases, Membrane-Associated
- Metalloendopeptidases
(genetics, metabolism)
- Nephritis, Hereditary
(genetics, pathology, physiopathology)
- RNA, Messenger
(analysis)
- X Chromosome
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