All issues > Volume 52(8); 2009

Original Article

Korean J Pediatr. 2009;52(8):944-952. Published online August 15, 2009.

Effect of angiotensin II inhibition on the epithelial to mesenchymal transition in developing rat kidney

Hyung Eun HE Yim¹, Kee Hwan KH Yoo¹, In Sun IS Bae¹, Young Sook YS Hong¹, Joo Won JW Lee¹

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

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

Abstract

Purpose
To investigate the effects of angiotensin II inhibition on the epithelial to mesenchymal transition (EMT) in the developing kidney, we tested the expression of EMT markers and nestin in angiotensin converting enzyme (ACE) inhibitor-treated kidneys.
Methods
Newborn rat pups were treated with enalapril (30 mg/kg/d) or a vehicle for 7 days. Immunohistochemistry for the expression of α-smooth muscle actin (SMA), E-cadherin, vimentin, and nestin were performed. The number of positively-stained cells was determined under 100 magnification in 10 random fields.
Results
In the enalapril-treated group, αSMA-positive cells were strongly expressed in the dilated tubular epithelial cells. The number of αSMA-positive cells in the enalapril-treated group increased in both the renal cortex and medulla, compared to the control group (P<0.05). The expression of E-cadherin-positive cells was dramatically reduced in the cortical and medullary tubular epithelial cells in the enalapril-treated group (P<0.05). The number of vimentin- and nestin-positive cells in the cortex was not different in comparisons between the two groups; however, their expression increased in the medullary tubulointerstitial cells in the enalapril-treated group (P<0.05).
Conclusion
Our results show that ACE inhibition in the developing kidney increases the renal EMT by up-regulating αSMA and down-regulating E-cadherin. Enalapril treatment was associated with increased expression of vimentin and nestin in the renal medulla, suggesting that renal medullary changes during the EMT might be more prominent, and ACE inhibition might differentially modulate the expression of EMT markers in the developing rat kidney.

Keywords :Angiotensin II, Cell Transdifferentiation, Growth and Development, Kidney Diseases