| Uric acid increases fibronectin synthesis through upregulation of lysyl oxidase expression in rat renal tubular epithelial cells. | |
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MedLine Citation:
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PMID: 20484295 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Urate is produced as the major end product of purine metabolism. In the last decade, the incidence of hyperuricemia increased markedly, and similar trends in the epidemiology of metabolic syndrome have been observed. Hyperuricemia is associated with renal disease, and recent studies have reported that mild hyperuricemia results in hypertension, intrarenal vascular disease, and renal injury. This has led to the hypothesis that uric acid may contribute to renal fibrosis and progressive renal disease. Our purpose was to investigate the relationship between uric acid and renal tubular injury. We applied the method of intraperitoneal injection of uric acid to generate the hyperuricemic mouse model. Compared with the saline injection group, the expression of lysyl oxidase (LOX) and fibronectin in kidneys was increased significantly in hyperuricemic groups. In vitro, uric acid significantly induced NRK-52E cells to express the ECM marker fibronectin, as well as LOX, which plays a pivotal role in ECM maturation, in a time- and dose-dependent manner. Upregulation of the urate transporter URAT1, which is located in the apical membrane of proximal tubules, sensitized the uric acid-induced fibronectin and LOX induction, while both knocking down URAT1 expression in tubular epithelial cells by RNA interference and inhibiting URAT1 function pharmacologically attenuated LOX and fibronectin expression. Furthermore, knockdown of LOX expression by a small interfering RNA strategy led to a decrease in fibronectin abundance induced by uric acid treatment. In addition, evidence of a uric acid-induced activation of the NF-kappaB signaling cascade was observed. Our findings highlight a need for carefully reevaluating our previous view on the pathological roles of hyperuricemia in the kidney and nephropathy induced by uric acid in clinical practice. |
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Authors:
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Zhou Yang; Wang Xiaohua; Jiang Lei; Tan Ruoyun; Xiong Mingxia; He Weichun; Fang Li; Wen Ping; Yang Junwei |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-19 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: 299 ISSN: 1522-1466 ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-04 Completed Date: 2010-09-03 Revised Date: 2011-04-28 |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: United States |
Other Details:
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Languages: eng Pagination: F336-46 Citation Subset: IM |
Affiliation:
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Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cell Line Disease Models, Animal Epithelial Cells / drug effects, enzymology*, pathology Extracellular Matrix Proteins / metabolism Fibronectins / metabolism* Fibrosis Fluorescent Antibody Technique Hyperuricemia / enzymology*, pathology Kidney Tubules / drug effects, enzymology*, pathology Male Mice Mice, Inbred C57BL NF-kappa B / metabolism Organic Anion Transporters / antagonists & inhibitors, genetics, metabolism Probenecid / pharmacology Protein-Lysine 6-Oxidase / genetics, metabolism* RNA Interference Rats Time Factors Up-Regulation Uric Acid / blood, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Extracellular Matrix Proteins; 0/Fibronectins; 0/NF-kappa B; 0/Organic Anion Transporters; 0/urate transporter; 149137-54-2/Lox protein, mouse; 57-66-9/Probenecid; 69-93-2/Uric Acid; EC 1.4.3.13/Protein-Lysine 6-Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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