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Expression change of Klotho in acute kidney injury induced by ischemia-reperfusion and its relationship with apoptosis

QIAN Ying-ying, YAN Yu-cheng, SHEN Yue, CHE Lin, GUAN Xue-jing, DAI Hui-li, GU Le-yi, WU Bei, NI Zhao-hui, QIAN Jia-qi   

  1. Renal Division, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Online:2014-06-28 Published:2014-06-30
  • Supported by:

    National Natural Science Foundation of China, 81170687; Medical Guidance Project of Science and Technology Commission of Shanghai Municipality, 134119a2300; Major Project of Science and Technology Commission of Shanghai Municipality, 12DJ1400200

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Abstract:

Objective To observe the expression change of Klotho in acute kidney injury (AKI) induced by ischemia-reperfusion and to explore the effects on the apoptosis of renal tubular epithelial cells. Methods Ten BALB/c mice were randomly divided into the ischemia-reperfusion group (I/R group, n=5) and sham-operation group (Sham group, n=5). The AKI model was established by bilateral renal pedicles clamping. The serum and renal issues of mice were collected after the model was established for 24 h. Levels of blood urea nitrogen and serum creatinine were detected by the enzymatic assay. The level of serum Klotho was measured by the ELISA. TUNEL staining was performed to assess the renal apoptosis. Expressions of genes and proteins of Klotho, Bax, Bcl-2, and Caspase-3 of renal tissues were detected by the Real-Time PCR and Western blotting. The relationship between the general and local levels of Klotho and the renal apoptosis was analyzed for mice with AKI by the Pearson line correlation method. Results Compared to the Sham group, renal tubular cells of mice of the I/R group significantly degenerated and necrotized; apoptotic cells increased significantly; and the level of cleaved Caspase-3 protein, Bax to Bcl-2 mRNA, and the protein ratios of renal tissues were significantly increased after 24 h of operations. The levels of serum Klotho of the I/R group were significantly lower than those of the Sham group [(669.89±136.51) pg/mL vs. (2 107.92±549.22) pg/mL, P<0.01]. The mRNA and protein expressions of renal Klotho were downregulated by approximately 90% (P<0.001) and 20% (P<0.05), respectively. The correlation analysis showed that the mRNA ratio of renal bax to bcl-2 was negatively correlated to both serum Klotho protein (r=-0.833, P<0.01) and renal klotho mRNA (r=-0.916, P<0.001). The renal Bax/Bcl-2 protein ratio was also significantly and negatively correlated to the renal Klotho protein (r=-0.637, P<0.05). Conclusion The general and local expressions of Klotho of mice with AKI induced by the ischemia-reperfusion decrease significantly, which may be closely related to the kidney injury induced by the apoptosis.

Key words: ischemia-reperfusion injury, acute kidney injury, Klotho, Bax/Bcl-2, apoptosis