Role of Fosinopril and Valsartan on Klotho Gene Expression Induced by Angiotensin II in Rat Renal Tubular Epithelial Cells

Kidney Blood Press Res. 2010;33(3):186-92. doi: 10.1159/000316703. Epub 2010 Jun 23.

Abstract

Background/aims: Klotho gene, a new anti-aging gene, is mainly expressed in the kidney tubules. Several studies have found the relationship between klotho and emergence and development of renal diseases. This study set out to explore the role of fosinopril (Fos) and valsartan (Val) on klotho expression induced by angiotensin II (Ang II) in rat renal tubular epithelial cells (NRK-52E).

Methods: NRK-52E cells were divided into five groups according to the treatment of Ang II, Fos and Val. Transforming growth factor-β1 (TGF-β1), p38, phospho-p38 (p-p38), p53, and Sp1 protein expression were determined by immunohistochemical and Western blotting analysis. Klotho expression was detected by reverse transcription-polymerase chain reaction and Western blotting analysis.

Results: Ang II upregulated TGF-β1, p-p38 and p53 expression, and inhibited Sp1 and klotho expression in NRK-52E cells. After the intervention of Fos and/or Val, TGF-β1, p-p38 and p53 expression were downregulated, Sp1 and klotho expression were upregulated. TGF-β1 and p53, Sp1 and klotho expression exhibited a positive linear correlation, respectively.

Conclusion: We conclude that Fos and Val have a protective role in Ang II-induced renal damage, and it may be through mechanism of inhibiting TGF-β1, p-p38 and p53 expression, thus upregulating Sp1 and klotho expression.

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Cell Line
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Fosinopril / pharmacology*
  • Gene Expression Regulation
  • Glucuronidase / biosynthesis*
  • Kidney Tubules / cytology
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism*
  • Rats
  • Tetrazoles / pharmacology*
  • Valine / analogs & derivatives*
  • Valine / pharmacology
  • Valsartan

Substances

  • Tetrazoles
  • Angiotensin II
  • Valsartan
  • Glucuronidase
  • klotho protein
  • Valine
  • Fosinopril