Antifibrotic Effects of Phosphodiesterase (PDE) Inhibitor in Experimental Interstitial Fibrosis induced by Unilateral Ureteral Obstruction.
- Author:
Il Soo HA
1
;
Eun Young UM
;
Hee Gyung KANG
;
Hye Won HAHN
;
Hye Won PARK
;
Hae Il CHEONG
;
Yong CHOI
Author Information
1. Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea. ilsooha@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Phosphodiesterase (PDE) inhibitor;
Cilostazol;
Dipyridamole;
Interstitial fibrosis;
Unilateral ureteral obstruction;
Rat
- MeSH:
Animals;
Connective Tissue Growth Factor;
Dipyridamole;
Drinking Water;
Enzyme-Linked Immunosorbent Assay;
Fibronectins;
Fibrosis*;
Ligation;
Rats;
Rats, Sprague-Dawley;
Transforming Growth Factor beta;
Transforming Growth Factor beta1;
Ureter*;
Ureteral Obstruction*
- From:Journal of the Korean Society of Pediatric Nephrology
2002;6(1):85-91
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Phosphodiesterase (PDE) inhibitor increases the cellular content of cAMP, and cAMP suppresses connective tissue growth factor (CTGF) expression induced by TGF-beta1. Therefore, we investigated whether PDE inhibitor suppresses renal fibrosis without suppression of TGF-beta. MATERIALS AND METHODS: Renal interstitial fibrosis was produced by ligation of left ureter in Sprague-Dawley rats. Cilostazol, a selective PDE3 inhibitor, and dipyridamole, a hybrid PDE5, PDE6, and PDE8 inhibitor, were provided in drinking water for 7 days. In addition to the Masson-trichrome score of renal tissue, the concentration of fibronectin and TGF-beta1 in renal tissue-conditioned media was measured by ELISA. RESULTS: Masson-trichrome score and fibronectin concentration were significantly lower in cilostazol-treated group compared to the control group (P<0.05). Though dipyridamole treatment seemed to suppress the Masson-trichrome score and fibronectin concentration too, the decrements were not statistically significant. There was no difference in TGF-beta1 concentration among the groups. CONCLUSION: A selective PDE3 inhibitor cilostazol suppresses renal fibrosis without alteration of TGF-beta expression.