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Interference in the nutrient-sensing and inflammatory signaling pathways by renal autophagy activation in mice with late stage diabetic nephropathy

  • Nephrology - Original Paper
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Abstract

Purpose

Disturbance in metabolism and inflammation are the main causes of kidney injury in patients with late stage diabetic nephropathy (DN). Here, we explored whether autophagy was activated in mice with late stage DN and whether it was associated with disturbance in metabolism and inflammation.

Methods

In total, mice were divided into the control group (db/m) and DN group (db/db). Mice were raised for 7 months, and their biochemical indices were measured. Subsequently, their kidneys were collected to detect autophagy and the related nutrient-sensing and inflammatory signaling pathways in late stage DN.

Results

The expression levels of autophagy markers LC3-I and LC3-II were significantly increased in mice with late stage DN, whereas that of autophagy flux marker P62 was significantly decreased, indicating activation of autophagy. Concurrently, mechanistic target of rapamycin was highly expressed as a cellular nutrient-sensing and energy regulator in mice with late stage DN. Additionally, the expression levels of markers of nutrient-sensing signaling pathways adenosine monophosphate-activated protein kinase (AMPK) were increased markedly in mice with late stage DN. Additionally, the expression levels of the marker of nutrient-sensing signaling pathways silent information regulator T1 (SIRT1), the marker of inflammatory signaling pathways high mobility group box protein 1 (HMGB1), and interferon regulatory factor 3 (IRF3) were significantly increased in mice with late stage DN.

Conclusions

The findings of our study indicate that autophagy activation in late stage DN may interfere with nutrient-sensing and inflammatory signaling pathways involving AMPK, SIRT1, HMGB1, and IRF3.

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Data availability

The data that support the findings of this study are available from the corresponding author upon request.

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Authors and Affiliations

  1. Department of Nephrology, First Medical Center of Chinese People’s Liberation Army General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, 100853, China

    Delun Li & Siyu Yuan

  2. Department of Nephrology, Guizhou Provincial People’s Hospital, Guiyang, 550002, China

    Yiyao Deng

Authors
  1. Delun Li
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  2. Siyu Yuan
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  3. Yiyao Deng
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Contributions

DL and YD designed the study. DL and SY wrote the manuscript. DL performed the experiments. DL, SY and YD supervised the study and edited the manuscript. All authors contributed to the manuscript and approved the submitted version.

Corresponding author

Correspondence to Yiyao Deng.

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Li, D., Yuan, S. & Deng, Y. Interference in the nutrient-sensing and inflammatory signaling pathways by renal autophagy activation in mice with late stage diabetic nephropathy. Int Urol Nephrol 56, 303–311 (2024). https://doi.org/10.1007/s11255-023-03687-x

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  • DOI: https://doi.org/10.1007/s11255-023-03687-x

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