| Protective effect of BMP-7 against aristolochic acid-induced renal tubular epithelial cell injury. | |
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MedLine Citation:
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PMID: 20696222 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Aristolochic acid nephropathy (AAN) is regarded as a kind of rapidly progressive renal fibrosis caused by the ingestion of herbal remedies containing aristolochic acid (AA). Recent studies showed that bone morphogenetic protein-7 (BMP-7) exerts beneficial effects on acute and chronic kidney injuries induced by different pathological conditions. We examined whether BMP-7 protects human renal tubular epithelial cells (HK-2) against AA-induced injury in vitro. HK-2 cells were cultured with different concentrations of AA and BMP-7 for 48h. Cell viability was determined by Cell Counting Kit-8 assay and lactate dehydrogenase (LDH) release. The apoptosis rate and the activity of caspase 3 protease were also examined. Epithelial-to-mesenchymal transition (EMT) was determined by cell morphology, E-cadherin and α-smooth muscle actin (α-SMA) protein expression, and TGF-β(1) and collagen III secretion. Additionally, the effect of anti-TGF-β1 antibody on AA-induced EMT was assessed. Our results indicated that BMP-7 significantly increased cell proliferation, decreased apoptosis rate and attenuated activation of caspase-3, resulting in the protection of HK-2 cells from AA-induced cytotoxicity. In addition, studies on EMT revealed that BMP-7 could inhibit AA-induced myofibroblast phenotype and restored the epithelial morphology in a dose-dependent manner. It was partially through reducing the activation of a myofibroblast phenotype and production TGF-β1. Treatment with neutralizing anti-TGF-β1 antibody also blocked AA-induced EMT and collagen III secretion. Together, these observations strongly suggest that BMP-7 is a potent inhibitor of AA-induced renal tubular epithelial cell injury and might be a promising agent for aristolochic acid-induced kidney damage. |
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Authors:
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Zihua Wang; Jinghong Zhao; Jing Zhang; Jing Wei; Jingbo Zhang; Yunjian Huang |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-07 |
Journal Detail:
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Title: Toxicology letters Volume: 198 ISSN: 1879-3169 ISO Abbreviation: Toxicol. Lett. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-14 Completed Date: 2010-10-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7709027 Medline TA: Toxicol Lett Country: Netherlands |
Other Details:
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Languages: eng Pagination: 348-57 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Institute of Nephrology of Chongqing, Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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physiology Aristolochic Acids / toxicity* Bone Morphogenetic Protein 7 / pharmacology* Cadherins / analysis, metabolism Caspase 3 / analysis, metabolism Cell Line Cell Survival / drug effects Collagen Type III / analysis, metabolism Epithelial Cells / drug effects Flow Cytometry Humans Kidney Tubules / cytology, drug effects* L-Lactate Dehydrogenase / analysis Microscopy, Fluorescence Microscopy, Phase-Contrast Transforming Growth Factor beta1 / analysis, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Aristolochic Acids; 0/Bone Morphogenetic Protein 7; 0/Cadherins; 0/Collagen Type III; 0/Transforming Growth Factor beta1; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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