Antibody to transforming growth factor-β ameliorates tubular apoptosis in unilateral ureteral obstruction

作者: Akira Miyajima , Jie Chen , Cathy Lawrence , Steve Ledbetter , Robert A. Soslow

DOI: 10.1046/J.1523-1755.2000.00414.X

关键词:

摘要: Antibody to transforming growth factor-β ameliorates tubular apoptosis in unilateral ureteral obstruction. Background Unilateral obstruction (UUO) is characterized by progressive renal atrophy, interstitial fibrosis, an increase (TGF-β), and apoptosis. The present study was undertaken determine the effect of a monoclonal antibody TGF-β (1D11) UUO. Methods Mechanical stretch applied epithelial cells (NRK-52E) computer-assisted system. Three doses 1D11 (either 0.5, 2, or 4 mg/rat) were administered rats one day prior UUO every two days thereafter, kidneys harvested at 13. Fibrosis assessed measuring tissue hydroxyproline mRNA for collagen fibronectin. Apoptosis with terminal deoxy transferase uridine triphosphate nick end-labeling assay. levels determined bioassay. Western blot immunostaining used identify proliferating cell nuclear antigen (PCNA), p53, bcl-2, inducible nitric oxide synthase (iNOS). Results Stretch significantly induced NRK-52E cells, which accompanied increased release TGF-β; (10 μg/mL) totally inhibited stretch-induced Control obstructed kidney contained 20-fold higher as compared its unobstructed kidney; neutralized kidney. exhibited more fibrosis than counterpart, blunted 1D11. In contrast, proliferation. p53 localized nuclei control diminished bcl-2 up-regulated 1D11-treated Total NOS activity iNOS treatment. Conclusion strongly suggests that promising agent prevent

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