Antifibrotic Effects of Phosphodiesterase (PDE) Inhibitor in Experimental Interstitial Fibrosis induced by Unilateral Ureteral Obstruction.

Ha, Il Soo; Um, Eun Young; Kang, Hee-Gyung; Hahn, Hye Won; Park, Hye Won; Cheong, Hae Il; Choi, Yong

J Korean Soc Pediatr Nephrol > Volume 6(1); 2002 > Article

J Korean Soc Pediatr Nephrol 2002;6(1): 85-91.

일측성 요로폐쇄에 의한 실험적 신 간질 섬유화에서 Phosphodiesterase(PDE) 억제제의 항 섬유화 작용

하일수, 엄은영, 강희경, 한혜원, 박혜원, 정해일, 최용

¹서울대학교 의과대학 소아과학교실
²서울대학교 의과대학 소아과학교실
³서울대학교 의과대학 소아과학교실
⁴서울대학교 의과대학 소아과학교실
⁵서울대학교 의과대학 소아과학교실
⁶서울대학교 의과대학 소아과학교실
⁷서울대학교 의과대학 소아과학교실

Antifibrotic Effects of Phosphodiesterase (PDE) Inhibitor in Experimental Interstitial Fibrosis induced by Unilateral Ureteral Obstruction.

Il Soo Ha, Eun Young Um, Hee-Gyung Kang, Hye Won Hahn, Hye Won Park, Hae Il Cheong, Yong Choi

¹Department of Pediatrics, Seoul National University College of Medicine
²Department of Pediatrics, Seoul National University College of Medicine
³Department of Pediatrics, Seoul National University College of Medicine
⁴Department of Pediatrics, Seoul National University College of Medicine
⁵Department of Pediatrics, Seoul National University College of Medicine
⁶Department of Pediatrics, Seoul National University College of Medicine
⁷Department of Pediatrics, Seoul National University College of Medicine

ABSTRACT

Purpose: Phosphodiesterase (PDE) inhibitor increases the cellular content of cAMP, and cAMP suppresses connective tissue growth factor (CTGF) expression induced by TGF-${beta}1$. Therefore, we investigated whether PDE inhibitor suppresses renal fibrosis without suppression of TGF-${beta}1$.
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-${beta}1$ 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-${beta}1$ concentration among the groups.
Conclusion : A selective PDE3 inhibitor cilostazol suppresses renal fibrosis without alteration of TGF-${beta}1$ expression. (J Korean Soc Pediatr Nephrol 2002 ;6 : 85-91)