Klotho reduces apoptosis in experimental ischaemic acute renal failure

Hidekazu Sugiura, Takumi Yoshida, Ken Tsuchiya, Michihiro Mitobe, Sayoko Nishimura, Satsuki Shirota, Takashi Akiba, Hiroshi Nihei

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2636-2645
Number of pages10
JournalNephrology Dialysis Transplantation
Volume20
Issue number12
DOIs
StatePublished - Dec 2005

Keywords

  • Adenovirus
  • Apoptosis
  • Ischemia reperfusion
  • Klotho

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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