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Rapamycin promotes podocyte autophagy and ameliorates renal injury in diabetic mice

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Abstract

The aim was to explore the effects of rapamycin on autophagy and injury of podocytes in streptozocin (STZ)-induced type 1 diabetic mice, and its role in delaying progression of diabetic nephropathy. In this study, male Balb/c mice were divided into three groups: control (n = 12), STZ-induced diabetic (n = 12), and rapamycin-treated diabetic (DM + Rapa) (n = 12), which received intraperitoneal injection of rapamycin (2 mg/kg/48 h) after induction of DM. Levels of urinary albumin (UA), blood urea nitrogen, serum creatinine, and kidney weight/body weight were measured at week 12. Renal pathologic changes, number of podocytes autophagy, and organelles injury were investigated by PAS staining, transmission electron microscopy, and immunofluorescence staining, respectively. Western blot was performed to determine the expression of LC3 (a podocyte autophagy marker), phosphorylated mammalian target of rapamycin, p-p70S6K, bax, and caspase-3 protein. Podocytes count was evaluated by immunofluorescence staining and Wilms tumor 1 immunohistochemistry, and Western blot of nephrin and podocin. The results indicated that rapamycin could reduce the kidney weight/body weight and UA secretion. It could alleviate podocyte foot process fusion, glomerular basement membrane thickening, and matrix accumulation, and increase the number of autophagosomes, and LC3-expressing podocytes. Down-regulation of bax and caspase-3 protein, and up-regulation of nephrin and podocin protein were observed in the glomeruli of diabetic mice after administration of rapamycin. In conclusion, rapamycin can ameliorate renal injury in diabetic mice by increasing the autophagy activity and inhibition of apoptosis of podocytes.

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Acknowledgments

This study was supported by research Grants from the National Natural Science Foundation of China (No. 81270290 and 30700316) and the project for overseas student from Ministry of Human Resources and Social Security of the People’s Republic of China.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Nephrology, Institute of Nephrology of Chongqing and Kidney Center of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People’s Republic of China

    Tangli Xiao, Xu Guan, Ling Nie, Lei Sun, Ting He, Yunjian Huang, Jingbo Zhang, Ke Yang & Jinghong Zhao

  2. State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury of PLA, Third Military Medical University, Chongqing, 400038, People’s Republic of China

    Song Wang & Junping Wang

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  1. Tangli Xiao
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  2. Xu Guan
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  3. Ling Nie
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  4. Song Wang
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  11. Jinghong Zhao
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Correspondence to Jinghong Zhao.

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Xiao, T., Guan, X., Nie, L. et al. Rapamycin promotes podocyte autophagy and ameliorates renal injury in diabetic mice. Mol Cell Biochem 394, 145–154 (2014). https://doi.org/10.1007/s11010-014-2090-7

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  • DOI: https://doi.org/10.1007/s11010-014-2090-7

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