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Augmenter of liver regeneration regulates autophagy in renal ischemia–reperfusion injury via the AMPK/mTOR pathway

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Abstract

Autophagy may have protective effects in renal ischemia–reperfusion (I/R) injury, although the underlying mechanisms remain unclear. Augmenter of liver regeneration (ALR), a widely distributed multifunctional protein that is originally identified as a hepatic growth factor, may participate in the process of autophagy. To investigate the role of ALR in autophagy, ALR expression is knocked-down in human kidney 2 (HK-2) cells with short hairpin RNA lentivirals. Then, the level of autophagy is measured in the shRNA/ALR group and the shRNA/control group in an in vitro model of ischemia–reperfusion (I/R). The results indicate that the level of autophagy in two groups increase, accompanied by increased reactive oxygen species production, especially in the shRNA/ALR group. The AMPK/mTOR signaling pathway is hyperactive in the shRNA/ALR group. Inhibition of autophagy with the AMPK inhibitor compound C induce apoptosis, especially in the shRNA/ALR group. These findings collectively indicate that ALR negatively regulates the autophagy process through an association with the AMPK/mTOR signaling pathway. Autophagy inhibit apoptosis and play a protective role under conditions of oxidative stress.

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Acknowledgements

This work was supported by Grants from the National Natural Science Foundation of China (81000299, 30971364), clinical medicine research special funds of the Chinese medical association (14050370574), Natural Science Foundation Project of CQ CSTC (cstc2015jcyjA10069), Grants from medical scientific research Projects of Chongqing health and family planning commission (20142031), the found for fostering talents in scientific research of chongqing medical university (201404), and a Grant from the science and technology department of Guizhou province, NO.LKZ(2012)27.

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Authors and Affiliations

  1. Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China

    Tao Pu, Hang Sun, Hui Guo, Xiao Jiang, Jun-bo Peng & Qi Liu

  2. Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China

    Tao Pu, Xiao-hui Liao & Ling Zhang

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  1. Tao Pu
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  2. Xiao-hui Liao
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  3. Hang Sun
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  7. Ling Zhang
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Correspondence to Ling Zhang or Qi Liu.

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Pu, T., Liao, Xh., Sun, H. et al. Augmenter of liver regeneration regulates autophagy in renal ischemia–reperfusion injury via the AMPK/mTOR pathway. Apoptosis 22, 955–969 (2017). https://doi.org/10.1007/s10495-017-1370-6

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