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Uric Acid-induced Phenotypic Transition of Renal Tubular Cells as a Novel Mechanism of Chronic Kidney Disease.
MedLine Citation:
PMID:  23283992     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Recent experimental and clinical studies suggest a causal role of uric acid in the development of chronic kidney disease. Most studies have focused on uric acid-induced endothelial dysfunction, oxidative stress and inflammation in the kidney. Direct effects of uric acid on tubular cells have not been studied in detail, and whether uric acid can mediate phenotypic transition of renal tubular cells such as epithelial-to-mesenchymal transition (EMT) is not known. We therefore investigated whether uric acid could alter E-cadherin expression and EMT in the kidney of of hyperuricemic rats and in cultured renal tubular cells (NRK cells). Experimental hyperuricemia was associated with evidence of EMT before the development of significant tubulointerstitial fibrosis at 4 weeks, as shown by decreased E-cadherin expression and an increased α-smooth muscle actin (α-SMA). Allopurinol significantly inhibited uric acid-induced changes in E-cadherin and α-SMA with an amelioration of renal fibrosis at 6 weeks. In cultured NRK cells, uric acid induced EMT which was blocked by the organic anion transport inhibitor, probenecid. Uric acid increased expression of transcriptional factors associated with decreased synthesis of E-cadherin (snail and slug). Uric acid also increased the degradation of E-cadherin via ubiquitination, which is of importance since downregulation of E-cadherin is considered to be a triggering mechanism for EMT. In conclusion, uric acid induces EMT of renal tubular cells decreasing E-cadherin synthesis via an activation of snail and slug as well as increasing the degradation of E-cadherin.
Authors:
Eun Sun Ryu; Mi Jin Kim; Hyun-Soo Shin; Yang-Hee Jang; Hack Sun Choi; Inho Jo; Richard J Johnson; Duk-Hee Kang
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-2
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  -     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Ewha Womans University School of Medicine.
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