Document Detail

Rosuvastatin inhibits pressure-induced fibrotic responses via the expression regulation of prostacyclin and prostaglandin E(2) in rat renal tubular cells.
MedLine Citation:
PMID:  23276663     Owner:  NLM     Status:  Publisher    
Statins are reported to alleviate renal fibrosis in animal models with ureteral obstruction. However, the molecular mechanism of this antifibrotic effect is still unclear. Pressure force is an important mechanism contributing to induction and progression of tubulointerstitial fibrogenesis in ureteric obstruction. In this study, we investigated the influence of rosuvastatin on pressure-induced fibrotic responses in rat renal tubular cells (NRK-52E). We established an in vitro pressure culture system to study pressure-induced fibrotic responses in NRK-52E cells. When NRK-52E cells were cultured in the pressure culture system, 60mmHg of pressure induced the expression of connective tissue growth factor (CTGF), transforming growth factor (TGF)-β, fibronectin, Smad3, and phospho-Smad3. Rosuvastatin significantly reduced these pressure-induced fibrotic responses at concentrations above 10μM. Rosuvastatin also reduced the TGF-β-induced expression of fibronectin and CTGF in NRK-52E cells. Pretreatment with rosuvastatin significantly induced prostacyclin (PGI(2)) generation, but reduced pressure-induced prostaglandin E(2) (PGE(2)). PGI(2) synthase small interfering RNA (siRNA) transfection significantly inhibited rosuvastatin-induced peroxisome proliferator-activated receptor α activation. The blockage of peroxisome proliferator-activated receptor α by siRNA transfection reduced the inhibitory effect of rosuvastatin on pressure-induced fibrotic responses. N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS398), a specific inhibitor of cyclooxygenase-2, diminished pressure-induced PGE(2) generation, and also reduced pressure-induced fibrotic responses. Additionally, PGE(2) decreased the antifibrotic effect of rosuvastatin. In conclusion, rosuvastatin reduces pressure-induced fibrotic responses in renal tubular cells by enhancing the PGI(2)- peroxisome proliferator-activated receptor α pathway and reducing PGE(2) generation.
Cheng-Hsien Chen; Chung-Yi Cheng; Yen-Cheng Chen; Yuh-Mou Sue; Yung-Ho Hsu; Wei-Lun Tsai; Tso-Hsiao Chen
Related Documents :
3161663 - Effects of synthetic atrial natriuretic peptide on renal function and renin release in ...
18838023 - Echocardiographic and morphological evaluation of the right heart after closure of atri...
11204293 - Factors affecting the difference between screening and home blood pressure measurements...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-28
Journal Detail:
Title:  European journal of pharmacology     Volume:  -     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2013-1-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  SMND-309 promotes angiogenesis in human umbilical vein endothelial cells through activating erythrop...
Next Document:  COsX-2-derived prostaglandins do not contribute to coronary flow regulation in diabetic rats: Distin...