Low-dose 5-aza-2'-deoxycytidine protects against early renal injury by increasing klotho expression
Yanlong Zhao1, Xiaorong Zeng1, Xinli Xu1
1Dialysis Department of Nephrology Hospital, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, Shaanxi, 710003, China.
Abstract:
Aim: To explore the effect of the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (Aza) on early renal injury. Materials & methods: Cell damage and inflammation are features of early renal injury. The apoptosis and inflammation in hypoxia/reoxygenation (H/R)-induced human proximal tubular epithelial cells (HK-2) and ischemia-reperfusion kidney were studied, and expression of the protein klotho was investigated. Results: Aza induced HK-2 apoptosis in a dose-dependent manner, but low-dose Aza attenuated the apoptosis and inflammation in H/R-induced HK-2 cells and ischemia-reperfusion kidney. Low-dose Aza ameliorated renal function in mice with renal ischemia-reperfusion injury. Meanwhile, low-dose Aza upregulated klotho expression in H/R-induced HK-2 cells and ischemia-reperfusion kidney. Klotho knockdown abrogated the effects of low-dose Aza on apoptosis and inflammation. Conclusion: Low-dose Aza protects against renal early injury by increasing klotho expression.
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