+ 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

Angiotensin II blockade upregulates the expression of Klotho, the anti-ageing gene, in an experimental model of chronic cyclosporine nephropathy



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



The Klotho gene plays a role in suppressing ageing-related disorders. It is suggested that activation of renin-angiotensin system (RAS) or oxidative stress suppresses Klotho in the kidney. This study evaluated the association between Klotho expression and RAS in cyclosporine (CsA)-induced renal injury. Chronic CsA nephropathy was induced by administering CsA (30 mg/kg) to mice on a low-salt diet (LSD) for 4 weeks. A normal-salt diet (NSD) was used as the control. Reverse transcription-polymerase chain reaction, western blot and immunohistochemistry were performed for Klotho and intrarenal RAS activity was measured using immunohistochemistry for angiotensinogen and renin. Oxidative stress was measured with urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG). CsA treatment decreased Klotho mRNA and protein in mouse kidney in a dose-dependent and time-dependent manner, but a concurrent treatment with losartan, an angiotensin II type 1 (AT1) receptor blocker, reversed the decrease in Klotho expression with histological improvement. This finding was more marked in the LSD than the NSD. Klotho expression was correlated with angiotensinogen and renin expression, tubulointerstitial fibrosis score and urinary 8-OHdG excretion. Angiotensin II may play a pivotal role in regulating Klotho expression in CsA-induced renal injury. AT1 receptor blocker may inhibit the ageing process by decreasing oxidative stress caused by CsA.

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

Accession: 051548689

Download citation: RISBibTeXText

PMID: 20813770

DOI: 10.1093/ndt/gfq537


Related references

Statin upregulates the expression of klotho, an anti-aging gene, in experimental cyclosporine nephropathy. Nephron. Experimental Nephrology 120(4): E123-E133, 2015

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

Blockade of angiotensin II with losartan attenuates transforming growth factor-beta1 inducible gene-h3 (betaig-h3) expression in a model of chronic cyclosporine nephrotoxicity. Nephron. Experimental Nephrology 99(1): E9-16, 2005

Angiotensin II receptor blockade with losartan protects epidermal growth factor expression in rat kidney with chronic cyclosporine nephropathy. Journal of the American Society of Nephrology 11(Program and Abstract Issue): 610A-611A, 2000

Regulation of multiple ageing-like phenotypes by inducible klotho gene expression in klotho mutant mice. Mechanisms of Ageing and Development 126(12): 1274-1283, 2005

Inhibitory effect of pravastatin on transforming growth factor beta1-inducible gene h3 expression in a rat model of chronic cyclosporine nephropathy. American Journal of Nephrology 25(6): 611-620, 2005

Angiotensin II blockage ameliorates fibrosis and decreases TGF-beta-1 expression in chronic cyclosporine nephropathy. Journal of the American Society of Nephrology 7(9): 1846, 1996

Influence of angiotensin II on expression of toll-like receptor 2 and maturation of dendritic cells in chronic cyclosporine nephropathy. Transplantation 83(7): 938-947, 2007

Angiotensin II blockade decreases TGF-beta1 and matrix proteins in cyclosporine nephropathy. Kidney International 52(3): 660-673, 1997

Nrf2 Deficiency Upregulates Intrarenal Angiotensin-Converting Enzyme-2 and Angiotensin 1-7 Receptor Expression and Attenuates Hypertension and Nephropathy in Diabetic Mice. Endocrinology 159(2): 836-852, 2017

Daidzein upregulates anti-aging protein Klotho and NaPi 2a cotransporter in a rat model of the andropause. Annals of Anatomy 221: 27-37, 2018

Angiotensin II blockade limits tubular protein overreabsorption and the consequent upregulation of endothelin 1 gene in experimental membranous nephropathy. Experimental Nephrology 6(2): 121-131, 1998

Upregulation of hyaluronan and its binding receptors in an experimental model of chronic cyclosporine nephropathy. Nephrology 15(2): 216-224, 2010

Comparison of early and late conversion of sirolimus in experimental model of chronic cyclosporine nephropathy. Journal of Korean Medical Science 27(2): 160-169, 2012

Angiotensin II receptor type I blockade reduces cyclosporine A nephropathy via downregulation of apoptotic genes in vivo. Journal of the American Society of Nephrology 10(PROGRAM AND ABSTR ISSUE): 653A, Sept, 1999