Int J Med Sci 2020; 17(17):2763-2772. doi:10.7150/ijms.49690

Research Paper

Klotho deficiency aggravates diabetes-induced podocyte injury due to DNA damage caused by mitochondrial dysfunction

Zhi Chen1, Qing Zhou2, Cong Liu3, Yiping Zeng4✉, Shaolong Yuan1✉

1. University-Town Clinic, 958 hospital of PLA Army, Chongqing, 400020, People's Republic of China.
2. School of Military Preventive Medicine, Army Military Medical University, Chongqing, 400020, People's Republic of China.
3. Center of Laboratory Medicine, Chongqing Prevention and Treatment Center for Occupational Disease, Chongqing, 400060, People's Republic of China.
4. Department of orthopedics, Chongqing general hospital, University of Chinese Academy of Sciences, Chongqing, 400014, People's Republic of China.

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Citation:
Chen Z, Zhou Q, Liu C, Zeng Y, Yuan S. Klotho deficiency aggravates diabetes-induced podocyte injury due to DNA damage caused by mitochondrial dysfunction. Int J Med Sci 2020; 17(17):2763-2772. doi:10.7150/ijms.49690. Available from http://www.medsci.org/v17p2763.htm

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Abstract

Diabetic nephropathy (DN) is a progressive disease, the main pathogeny of which is podocyte injury inducing glomerular filtration barrier and proteinuria. The occurrence and development of DN could be partly attributed to the reactive oxygen species (ROS) generated by mitochondria. However, research on how mitochondrial dysfunction (MtD) ultimately causes DNA damage is poor. Here, we investigated the influence of Klotho deficiency on high glucose (HG)-induced DNA damage in vivo and in vitro. First, we found that the absence of Klotho aggravated diabetic phenotypes indicated by podocyte injury accompanied by elevated urea albumin creatinine ratio (UACR), creatinine and urea nitrogen. Then, we further confirmed that Klotho deficiency could significantly aggravate DNA damage by increasing 8-OHdG and reducing OGG1. Finally, we demonstrated Klotho deficiency may promote MtD to promote 8-OHdG-induced podocyte injury. Therefore, we came to a conclusion that Klotho deficiency may promote diabetes-induced podocytic MtD and aggravate 8-OHdG-induced DNA damage by affecting OOG1.

Keywords: Klotho, diabetes, mitochondrial dysfunction (MtD), podocyte injury, DNA damage