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Uric acid-induced phenotypic transition of renal tubular cells as a novel mechanism of chronic kidney disease

Title
Uric acid-induced phenotypic transition of renal tubular cells as a novel mechanism of chronic kidney disease
Authors
Ryu E.-S.Kim M.J.Shin H.-S.Jang Y.-H.Choi H.S.Jo I.Johnson R.J.Kang D.-H.
Ewha Authors
강덕희조인호최학선
SCOPUS Author ID
강덕희scopus; 조인호scopus
Issue Date
2013
Journal Title
American Journal of Physiology - Renal Physiology
ISSN
0363-6127JCR Link
Citation
vol. 304, no. 5, pp. F471 - F480
Indexed
SCOPUS WOS scopus
Abstract
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 acidinduced endothelial dysfunction, oxidative stress, and inflammation in the kidney. The 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 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 wk, 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 wk. 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 Ecadherin 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. © 2013 the American Physiological Society.
DOI
10.1152/ajprenal.00560.2012
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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