Klotho reduces apoptosis in experimental ischaemic acute kidney injury via HSP-70.
BACKGROUND
High Klotho expression has been detected in the kidney, and since the results of a recent study suggested that Klotho induction mitigates ischaemic damage in the kidney, in the present study we explored the mechanism by which Klotho expression reduces renal ischaemia-reperfusion injury (IRI).


METHODS
Male mice were subjected to bilateral renal ischaemia for 30 min and reperfusion for 24 h, or to a sham operation. Both the IRI group and the sham group were intravenously injected with an adenovirus harbouring the mouse Klotho gene (ad-kl) before renal IRI. In addition, mIMCD3 cells induced to overexpress Klotho by transferring the Klotho gene with ad-kl were analysed by DNA microarray and real-time PCR. Renal expression of Klotho and several genes selected by DNA microarray were assessed by real-time PCR or Western blotting, and TUNEL staining was performed to assess apoptosis.


RESULTS
Prior administration of ad-kl to the mice resulted in robust induction of Klotho mRNA in the kidney and liver. Ad-kl transfer improved the plasma creatinine values and mitigated the histological damage and apoptosis induced by IRI. Expression of several genes was altered in mIMCD3 cells as a result of the change in Klotho expression, and expression of heat shock protein 70 (HSP70), in particular, was up-regulated in ad-kl mouse kidneys and HK2 cells.


CONCLUSIONS
The results suggest that Klotho is involved in the pathophysiology of IRI. Klotho mitigates apoptosis in experimental ischaemic acute kidney injury via expression of HSP70.
Sugiura
Hidekazu
H
Department of Medicine IV, Tokyo Women's Medical University, Tokyo, Japan.
Yoshida
Takumi
T
Mitobe
Michihiro
M
Yoshida
Satsuki
S
Shiohira
Shunji
S
Nitta
Kosaku
K
Tsuchiya
Ken
K
D058186:Acute Kidney Injury / Q000378:metabolism* / Q000473:pathology; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D004195:Disease Models, Animal; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007679:Kidney Medulla / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D000090265:Klotho Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D015854:Up-Regulation
D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D005966:Glucuronidase; D000090265:Klotho Proteins