Melatonin attenuates renal fibrosis in diabetic mice by activating the AMPK/PGC1α signaling pathway and rescuing mitochondrial function

  • Authors:
    • Jian Li
    • Nan Li
    • Shuangtong Yan
    • Yanhui Lu
    • Xinyu Miao
    • Zhaoyan Gu
    • Yinghong Shao
  • View Affiliations

  • Published online on: November 29, 2018     https://doi.org/10.3892/mmr.2018.9708
  • Pages: 1318-1330
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Abstract

Mitochondrial homeostasis is a highly regulated process that serves a critical role in the maintenance of renal structure and function. The growing interest in the field of mitochondrial homeostasis promises to provide more information regarding the mechanisms involved in diabetic renal fibrosis, and aid in the development of novel strategies to combat the disease. In the present study, the effects of melatonin on renal damage in mice with diabetes were evaluated and the underlying mechanisms were investigated. Cellular apoptosis was determined using TUNEL assay and western blotting. Mitochondrial function was measured using fluorescence assay and western blotting. The results indicated that diabetic renal fibrosis was associated with 5'adenosine monophosphate‑activated protein kinase (AMPK) downregulation. However, melatonin administration rescued AMPK activity, reduced diabetic renal fibrosis, alleviated glomerular apoptosis and preserved kidney function. The functional experiments demonstrated that melatonin‑induced AMPK activation enhanced peroxisome proliferator‑activated receptor γ coactivator 1‑α (PGC1α) expression, sustained mitochondrial function and blocked mitochondrial apoptosis, leading to protection of the glomerulus against glucotoxicity. However, loss of AMPK and PGC1α negated the protective effects of melatonin on mitochondrial homeostasis, glomerular survival and diabetic renal fibrosis. In summary, the present study revealed that melatonin rescued impaired mitochondrial function and reduced glomerular apoptosis in the context of diabetic renal fibrosis by activating the AMPK/PGC1α pathway.
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February-2019
Volume 19 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Li J, Li N, Yan S, Lu Y, Miao X, Gu Z and Shao Y: Melatonin attenuates renal fibrosis in diabetic mice by activating the AMPK/PGC1α signaling pathway and rescuing mitochondrial function. Mol Med Rep 19: 1318-1330, 2019
APA
Li, J., Li, N., Yan, S., Lu, Y., Miao, X., Gu, Z., & Shao, Y. (2019). Melatonin attenuates renal fibrosis in diabetic mice by activating the AMPK/PGC1α signaling pathway and rescuing mitochondrial function. Molecular Medicine Reports, 19, 1318-1330. https://doi.org/10.3892/mmr.2018.9708
MLA
Li, J., Li, N., Yan, S., Lu, Y., Miao, X., Gu, Z., Shao, Y."Melatonin attenuates renal fibrosis in diabetic mice by activating the AMPK/PGC1α signaling pathway and rescuing mitochondrial function". Molecular Medicine Reports 19.2 (2019): 1318-1330.
Chicago
Li, J., Li, N., Yan, S., Lu, Y., Miao, X., Gu, Z., Shao, Y."Melatonin attenuates renal fibrosis in diabetic mice by activating the AMPK/PGC1α signaling pathway and rescuing mitochondrial function". Molecular Medicine Reports 19, no. 2 (2019): 1318-1330. https://doi.org/10.3892/mmr.2018.9708