Abstract | BACKGROUND: METHODS: RESULTS: Stretch significantly induced apoptosis in NRK-52E cells, which was accompanied by an increased release of TGF-beta; 1D11 (10 microg/mL) totally inhibited stretch-induced apoptosis. Control obstructed kidney contained 20-fold higher TGF-beta as compared with its unobstructed kidney; 1D11 neutralized tissue TGF-beta of the obstructed kidney. Control obstructed kidney exhibited significantly more fibrosis and tubular apoptosis than its unobstructed counterpart, which was blunted by 1D11. In contrast, 1D11 significantly increased tubular proliferation. p53 immunostaining was localized to renal tubular nuclei of control obstructed kidney and was diminished by 1D11. In contrast, bcl-2 was up-regulated in the 1D11-treated obstructed kidney. Total NOS activity and iNOS activity of the obstructed kidney were increased by 1D11 treatment. CONCLUSION: The present study strongly suggests that an antibody to TGF-beta is a promising agent to prevent renal tubular fibrosis and apoptosis in UUO.
|
Authors | A Miyajima, J Chen, C Lawrence, S Ledbetter, R A Soslow, J Stern, S Jha, J Pigato, M L Lemer, D P Poppas, E D Vaughan, D Felsen |
Journal | Kidney international
(Kidney Int)
Vol. 58
Issue 6
Pg. 2301-13
(Dec 2000)
ISSN: 0085-2538 [Print] United States |
PMID | 11115064
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antibodies, Monoclonal
- Proliferating Cell Nuclear Antigen
- Proto-Oncogene Proteins c-bcl-2
- Transforming Growth Factor beta
- Tumor Suppressor Protein p53
- Citrulline
- Nitric Oxide
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type II
- Nos2 protein, rat
|
Topics |
- Animals
- Antibodies, Monoclonal
(pharmacology)
- Apoptosis
- Atrophy
- Blotting, Western
- Cell Line
- Citrulline
- Fibrosis
- Gene Expression Regulation, Enzymologic
- In Situ Nick-End Labeling
- Kidney Tubules
(chemistry, enzymology, pathology)
- Nephritis, Interstitial
(pathology, prevention & control, therapy)
- Nitric Oxide
(metabolism)
- Nitric Oxide Synthase
(analysis, genetics, metabolism)
- Nitric Oxide Synthase Type II
- Proliferating Cell Nuclear Antigen
(genetics)
- Proto-Oncogene Proteins c-bcl-2
(analysis)
- Rats
- Rats, Sprague-Dawley
- Stress, Mechanical
- Transforming Growth Factor beta
(analysis, immunology, metabolism)
- Tumor Suppressor Protein p53
(analysis)
- Ureteral Obstruction
(pathology, prevention & control, therapy)
|