Klotho reduces apoptosis in experimental ischaemic acute renal failure.
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.


CONCLUSIONS
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.
Sugiura
Hidekazu
H
Department of Blood Purification, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-city, Tokyo 162-8666, Japan.
Yoshida
Takumi
T
Tsuchiya
Ken
K
Mitobe
Michihiro
M
Nishimura
Sayoko
S
Shirota
Satsuki
S
Akiba
Takashi
T
Nihei
Hiroshi
H
D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D015870:Gene Expression; D005966:Glucuronidase; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D000090265:Klotho Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012313:RNA / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008565:Membrane Proteins; D012313:RNA; D005966:Glucuronidase; D000090265:Klotho Proteins