Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Jan;21(1):105-9.
doi: 10.1053/j.jrn.2010.10.020.

Indoxyl sulfate reduces klotho expression and promotes senescence in the kidneys of hypertensive rats

Ayinuer Adijiang  1 , Hidehisa Shimizu, Yusuke Higuchi, Fuyuhiko Nishijima, Toshimitsu Niwa
Affiliations

Indoxyl sulfate reduces klotho expression and promotes senescence in the kidneys of hypertensive rats

Ayinuer Adijiang et al. J Ren Nutr. 2011 Jan.

Abstract

Background: Administration of indoxyl sulfate, a uremic toxin, promotes progression of chronic kidney disease in rats affected by the disease. Klotho, an anti-aging gene, is expressed in the kidneys, and its renal expression is decreased in chronic kidney disease. This study aimed to clarify whether indoxyl sulfate could reduce klotho expression and contribute to cell senescence in the kidneys of hypertensive rats.

Methods: The rats used for this study were segregated in to the following 4 groups: (1) Dahl salt-resistant normotensive rats (DN), (2) Dahl salt-resistant normotensive indoxyl sulfate-administered rats (DN + IS), (3) Dahl salt-sensitive hypertensive rats (DH), and (4) Dahl salt-sensitive hypertensive indoxyl sulfate-administered rats (DH + IS). After 32 weeks, their kidneys were excised for histological and immunohistochemical analysis for klotho, senescence-associated β-galactosidase, p16(INK4a), p21(WAF1/CIP1), p53, and retinoblastoma protein (Rb).

Results: DH + IS rats showed decreased expression of klotho, increased expression of senescence-associated β-galactosidase, p16(INK4a), p21(WAF1/CIP1), p53, and Rb in renal tubular cells, and increased tubulointerstitial fibrosis and mesangial expansion as compared with DH rats. Further, DN + IS rats showed decreased expression of klotho as compared with DN rats.

Conclusion: Administration of indoxyl sulfate to hypertensive rats reduced renal expression of klotho and promoted cell senescence with expression of senescence-related proteins, such as p16(INK4a), p21(WAF1/CIP1), p53, and Rb, which was accompanied by renal fibrosis.

PubMed Disclaimer