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. CONCLUSION: 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.
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 mouseKlotho 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-klmouse kidneys and HK2 cells. CONCLUSION: 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.
Authors: Eman A Elghoroury; Fatina I Fadel; Manal F Elshamaa; Dina Kandil; Doaa M Salah; Marwa M El-Sonbaty; Hebatallah Farouk; Mona Raafat; Soha Nasr Journal: Pediatr Nephrol Date: 2018-01-08 Impact factor: 3.714
Authors: Anders Nordholm; Maria L Mace; Eva Gravesen; Jacob Hofman-Bang; Marya Morevati; Klaus Olgaard; Ewa Lewin Journal: Am J Physiol Renal Physiol Date: 2017-11-29
Authors: Ming Chang Hu; Mingjun Shi; Jianning Zhang; Tayo Addo; Han Ju Cho; Sarah L Barker; Priya Ravikumar; Nancy Gillings; Ao Bian; Sachdev S Sidhu; Makoto Kuro-o; Orson W Moe Journal: J Am Soc Nephrol Date: 2015-05-14 Impact factor: 10.121
Authors: Seok-Jo Kim; Paul Cheresh; Mesut Eren; Renea P Jablonski; Anjana Yeldandi; Karen M Ridge; G R Scott Budinger; Dong-Hyun Kim; Myles Wolf; Douglas E Vaughan; David W Kamp Journal: Am J Physiol Lung Cell Mol Physiol Date: 2017-04-20 Impact factor: 5.464