+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Statin upregulates the expression of klotho, an anti-aging gene, in experimental cyclosporine nephropathy



Statin upregulates the expression of klotho, an anti-aging gene, in experimental cyclosporine nephropathy



Nephron. Experimental Nephrology 120(4): E123-E133



We recently reported that long-term cyclosporine (CsA)-induced oxidative stress is associated with decreased expression of klotho, an anti-aging gene. This study evaluated whether the antioxidant effect of statin might upregulate klotho expression in CsA-induced renal injury. Two separate experiments were performed. First, the dose-dependent effect of statin on klotho expression was evaluated in normal mouse kidneys. Second, the effect of statin on klotho expression was evaluated in experimental chronic CsA nephropathy in mice. We performed immunohistochemistry and immunoblotting for klotho, Forkhead box O transcription factors [FoxOs; phosphorylated FoxO1 (p-FoxO1) and FoxO3a (p-FoxO3a)] and their target molecules, manganese superoxide dismutase (MnSOD), Bim and hemeoxygenase-1. Statin treatment upregulated klotho expression in a dose-dependent manner in the normal mouse kidney and alleviated the decrease in klotho expression in kidneys exhibiting CsA nephropathy. CsA administration increased p-FoxO1 expression and decreased p-FoxO3a expression, whereas concurrent statin treatment reversed these changes, increased the expression of the antioxidant enzymes MnSOD and hemeoxygenase-1 and decreased the expression of the pro-apoptotic protein Bim. Statin-mediated upregulation of klotho expression and differential regulation of FoxO expression promote resistance to CsA-induced oxidative stress.

(PDF emailed within 0-6 h: $19.90)

Accession: 055911366

Download citation: RISBibTeXText

PMID: 22986347

DOI: 10.1159/000342117


Related references

Angiotensin II blockade upregulates the expression of Klotho, the anti-ageing gene, in an experimental model of chronic cyclosporine nephropathy. Nephrology, Dialysis, Transplantation 26(3): 800-813, 2011

Influence of N-acetylcysteine on Klotho expression and its signaling pathway in experimental model of chronic cyclosporine nephropathy in mice. Transplantation 96(2): 146-153, 2013

Genetic deficiency of anti-aging gene klotho exacerbates early nephropathy in STZ-induced diabetes in male mice. Endocrinology 154(10): 3855-3863, 2013

Daidzein upregulates anti-aging protein Klotho and NaPi 2a cotransporter in a rat model of the andropause. Annals of Anatomy, 2018

Effects of intra- and extracellular factors on anti-aging klotho gene expression. Genetics and Molecular Research 10(3): 2009-2023, 2012

Vitamin D receptor controls expression of the anti-aging klotho gene in mouse and human renal cells. Biochemical and Biophysical Research Communications 414(3): 557-562, 2011

Testosterone increases renal anti-aging klotho gene expression via the androgen receptor-mediated pathway. Biochemical Journal 464(2): 221-229, 2015

Resveratrol increases anti-aging Klotho gene expression via the activating transcription factor 3/c-Jun complex-mediated signaling pathway. International Journal of Biochemistry & Cell Biology 53: 361-371, 2015

Studies on the anti-aging activity of a glycoprotein isolated from Fupenzi (Rubus chingii Hu.) and its regulation on klotho gene expression in mice kidney. International Journal of Biological Macromolecules 119: 470-476, 2018

Regulation of S-formylglutathione hydrolase by the anti-aging gene klotho. Oncotarget 8(51): 88259-88275, 2017

Pulmonary emphysema in klotho mutant mice (deficient in klotho gene expression): klotho gene essential in postnatal pulmonary integrity. Nihon Kokyuki Gakkai Zasshi 40(3): 203-209, 2002

Characterization of the expression of the anti-aging protein Klotho in rodent and primate brain. 2007

The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma. Molecular Cancer 9(): 109-109, 2010

Induction of anti-aging gene klotho with a small chemical compound that demethylates CpG islands. Oncotarget 8(29): 46745-46755, 2017

Klotho ameliorates cyclosporine A-induced nephropathy via PDLIM2/NF-kB p65 signaling pathway. Biochemical and Biophysical Research Communications 486(2): 451-457, 2017