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

Korean Journal of Pediatrics 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 Yim, Kee Hwan Yoo, In Sun Bae, Young Sook Hong, Joo Won Lee
Department of Pediatrics, College of Medicine, Korea University, Seoul, Korea
발생 중인 백서 신장에서 Angiotensin II 억제가 epithelial to mesenchymal transition에 미치는 효과
임형은, 유기환, 배인순, 홍영숙, 이주원
고려대학교 의과대학 소아과학교실
Correspondence: 
Kee Hwan 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.
Key Words: Angiotensin II, Cell Transdifferentiation, Growth and Development, Kidney Diseases


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