NDT Advance Access published online on October 4, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfi165
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1 Department of Medicine IV, Tokyo Women's Medical University, Tokyo, Japan
* To whom correspondence should be addressed. Background. Klotho is associated with the suppression of several ageing phenotypes. Because high klotho gene expression was detected in the kidney and several studies have found altered expression in animal models, we explored the physiological relevance of klotho expression in the kidney under renal ischemia reperfusion injury (IRI). Methods. Male Wistar rats were subjected to bilateral renal ischemia or sham operation, followed by reperfusion for 6, 12 or 24 h, or 2 to 10 days. Renal expression of klotho was assessed by real-time PCR or Western blotting. Creatinine levels were determined. Immunohistochemical studies and TUNEL staining were performed. An adenovirus harbouring the mouse klotho gene (ad-kl) was intravenously administered to one group of rats before renal IRI. Results. Renal klotho mRNA and protein expressions were significantly reduced in IRI rats the first day after ischemia. Pre-treatment with ad-kl resulted in a robust induction of klotho mRNA and protein in the liver but not in the kidney. Ad-kl gene transfer improved serum creatinine and the histological changes. Apoptosis induced by IRI was attenuated following ad-kl administration. Conclusion. The data suggest klotho to be involved in the pathophysiology of IRI. Downregulation of renal klotho exacerbates ischaemic acute renal failure, and klotho gene induction has therapeutic potential in managing ischaemic renal damage.
Received December 20, 2004
Accepted August 30, 2005
Original Articles
Klotho reduces apoptosis in experimental ischaemic acute renal failure
2 Department of Medicine IV, Tokyo Women's Medical University, Tokyo, Japan; Department of Blood Purification, Tokyo Women's Medical University, Tokyo, Japan
Takumi Yoshida, E-mail: tyoshida{at}kc.twmu.ac.jp
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