Korean J Pediatr.  2009 Aug;52(8):944-952. 10.3345/kjp.2009.52.8.944.

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

• Yim HE
• Yoo KH
• Bae IS
• Hong YS
• Lee JW

• KMID: 2281596
• DOI: http://doi.org/10.3345/kjp.2009.52.8.944

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 alpha-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, alphaSMA-positive cells were strongly expressed in the dilated tubular epithelial cells. The number of alphaSMA-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-regulatingalphaSMA 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.

Keyword

Angiotensin II; Cell Transdifferentiation; Growth and Development; Kidney Diseases

MeSH Terms

Actins
Angiotensin II
Angiotensins
Animals
Cadherins
Cell Transdifferentiation
Enalapril
Epithelial Cells
Growth and Development
Humans
Immunohistochemistry
Infant, Newborn
Intermediate Filament Proteins
Kidney
Kidney Diseases
Muscles
Nerve Tissue Proteins
Peptidyl-Dipeptidase A
Rats
Vimentin
Actins
Angiotensin II
Angiotensins
Cadherins
Enalapril
Intermediate Filament Proteins
Nerve Tissue Proteins
Peptidyl-Dipeptidase A
Vimentin