All issues > Volume 47(4); 2004

Original Article

Korean J Pediatr. 2004;47(4):430-438. Published online April 15, 2004.

Phenotypic Transformation of Tubular Epithelial Cells and Fibroblasts Following Unilateral Ureteral Obstruction or Angiotensin II Infusion in the S-D Rat

Eui Seong ES Lee¹, Min Jee MJ Jeoung¹, Kee Hwan KH Yoo¹, Young Sook YS Hong¹, Joo Won JW Lee¹, Soon Kyum SK Kim¹

¹Department of Pediatrics, College of Medicine, Korea University, Guro Hospital, Seoul, Korea

Correspondence Kee Hwan KH Yoo ,Email: guroped@korea.ac.kr

Abstract

Purpose
: Unilateral ureteral obstruction(UUO), a well established experimental model of renal injury, gives rise to tubulointerstitial fibrosis, tubular dilatation and cellular atrophy. Angiotensin(ANG) II may take the prime role in the regulation of this response. The objectives in the current investigation were to determine whether the renal response to UUO involves the dedifferentiation of tubular epithelial cells to mesenchymal cells(expressing vimentin, V) whether the response implicates the transformation of fibroblasts to myofibroblasts(expressing α-smooth muscle actin, SMA), and whether these responses depend on the action of ANG II or not.
Methods
: Unilateral ureteral ligation and sham operations were performed in 12 adult male Sprague- Dawley rats. An additional 18 rats received exogenous ANG II at 50 ng/min or vehicle for one week using an osmotic minipump inserted into the interscapular area. Rats were sacrificed on postoperative day seven or day 14. To know the expression of vimentin(V) and α-smooth muscle actin (SMA) proteins, immunohistochemical staining and Western blot assay were done.
Results
: In immunohistochemical staining, following UUO, V-positive cells appeared markedly in the interstitium and tubular cells within dilated tubules. UUO also markedly increased α-SMA expression in the interstitium surrounding dilated tubules. In Western blotting, UUO increased V(five times of Sham) and α-SMA(2.5 times of Sham) expression. ANG II infusion increased α-SMA significantly(two times of control), but not V expression in Western blotting.
Conclusion
: Phenotypic transformation of fibroblasts to myofibroblasts following UUO may depend on ANG II, but dedifferentiation of tubular epithelial cells may depend on other mechanisms rather than ANG II.

Keywords :Unilateral ureteral obstruction, Angiotensin II, Tubular epithelial cell, Fibroblast, Transformation