Low-dose 5-aza-2′-deoxycytidine protects against early renal injury by increasing klotho expression

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.