| Inhibition of tubulointerstitial fibrosis by pentoxifylline is associated with improvement of vascular endothelial growth factor expression. | |
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MedLine Citation:
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PMID: 19079293 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIM: Recent information indicates that pentoxifylline (PTX) has the ability to suppress inflammation and profibrotic cell proliferation. In this study, we investigated the effect of PTX on tubulointerstitial fibrosis and the expression of vascular endothelial growth factor (VEGF) in a rat model of obstructive nephropathy. METHODS: Wistar rats with left ureteral ligation were divided into control and PTX-treated groups. The histopathologic degree of tubulointerstitial fibrosis was scored with PAS and Masson-stained sections. The protein and mRNA for vascular endothelial growth factor (VEGF) were semiquantitatively measured with immunohistochemistry and RT-PCR. The protein for transforming growth factor beta1 (TGFbeta1) and hypoxia-induced factor 1 alpha (HIF-1alpha) was determined by Western blot. RESULTS: Compared with the control group, PTX treatment reduced fibrosis scores at d 7 and d 14 (P<0.05). The reduction was accompanied by inhibited expression of transforming growth factor-beta 1 (TGFbeta1), a key cytokine in tubulointerstitial fibrogenesis (P<0.01). Meanwhile, VEGF protein and mRNA in the kidney were increased in the PTX-treated group compared with the control group (P<0.01). PTX up-regulated expression of VEGF mRNA in a dose- and time-dependent manner in cultured HK-2 cells (P<0.01). However, expression of HIF-1alpha (a key transcription factor for VEGF gene expression) was unchanged by PTX treatment. PTX prolonged the half-life of VEGF mRNA by a 1.07-fold increase. CONCLUSIONS: PTX inhibited tubulointerstitial fibrosis in a rat model of obstructive nephropathy while preventing loss of VEGF. PTX up-regulated expression of VEGF mRNA through stabilization of its mRNA in cultured renal tubular epithelial cells. |
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Authors:
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Qiu-gen Zhou; Fa-lei Zheng; Fan-fan Hou |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-12-15 |
Journal Detail:
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Title: Acta pharmacologica Sinica Volume: 30 ISSN: 1745-7254 ISO Abbreviation: Acta Pharmacol. Sin. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2009-01-06 Completed Date: 2009-04-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100956087 Medline TA: Acta Pharmacol Sin Country: China |
Other Details:
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Languages: eng Pagination: 98-106 Citation Subset: IM |
Affiliation:
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Division of Nephrology, Southern Medical University Nanfang Hospital, Guangzhou 510515, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Disease Models, Animal Female Fibrosis* / drug therapy, pathology Humans Hypoxia-Inducible Factor 1, alpha Subunit / genetics, metabolism Kidney Tubules, Proximal / drug effects, metabolism, pathology* Nephritis, Interstitial* / drug therapy, pathology Pentoxifylline / pharmacology, therapeutic use* Random Allocation Rats Rats, Wistar Transforming Growth Factor beta1 / genetics, metabolism Vascular Endothelial Growth Factor A / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Transforming Growth Factor beta1; 0/Vascular Endothelial Growth Factor A; 6493-05-6/Pentoxifylline |
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