Abstract | BACKGROUND: Many forms of glomerular diseases are characterized by injury to the glomerular visceral epithelial cell, or podocyte, which usually results in depletion of podocyte number. However, in diseases where podocyte proliferation occurs there is a rapid decline in renal function. The consequences of inhibiting podocyte proliferation on renal function have not been fully established. At the level of the cell cycle, cyclin-dependent kinase 2 (CDK2) is required for proliferation. METHODS: RESULTS: Inhibiting CDK2 activity resulted in a marked decrease in glomerular DNA synthesis [5-bromo-2'-deoxyridine ( BrdU) staining] in Roscovitine-treated animals at day 5 of nephritis (P < 0.05 versus control). This was associated with a significant decrease in BUN and glomerulosclerosis at day 14 (P < 0.01 versus control) and a decrease in the accumulation of the extracellular matrix protein laminin (P < 0.01 versus control). CONCLUSION: Inhibiting podocyte proliferation in experimental glomerulonephritis is associated with improvement in renal function and histology, suggesting that inhibiting CDK2 activity is a potential therapeutic target for glomerular diseases characterized by podocyte proliferation.
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Authors | Siân V Griffin, Ronald D Krofft, Jeffrey W Pippin, Stuart J Shankland |
Journal | Kidney international
(Kidney Int)
Vol. 67
Issue 3
Pg. 977-86
(Mar 2005)
ISSN: 0085-2538 [Print] United States |
PMID | 15698436
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Extracellular Matrix Proteins
- Purines
- Roscovitine
- DNA
- CDC2-CDC28 Kinases
- Cdk2 protein, mouse
- Cyclin-Dependent Kinase 2
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Topics |
- Animals
- CDC2-CDC28 Kinases
(metabolism)
- Cell Proliferation
- Cyclin-Dependent Kinase 2
- DNA
(biosynthesis)
- Epithelial Cells
(cytology)
- Extracellular Matrix Proteins
(metabolism)
- Glomerulonephritis
(pathology, physiopathology)
- Kidney
(physiopathology)
- Kidney Glomerulus
(cytology)
- Male
- Mice
- Mice, Inbred C57BL
- Purines
(pharmacology)
- Roscovitine
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