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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
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Interference in the nutrient-sensing and inflammatory signaling pathways by renal autophagy activation in mice with

Delun Li1, Siyu Yuan1, Yiyao Deng2

  • 1Department 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.

International Urology and Nephrology
|June 24, 2023
PubMed
Abstract

Insights

Autophagy is activated in late-stage diabetic nephropathy (DN), impacting nutrient-sensing and inflammatory pathways. This study investigated autophagy

Area of Science:

  • Nephrology
  • Metabolic Disorders
  • Cellular Biology

Background:

  • Diabetic nephropathy (DN) involves metabolic and inflammatory disturbances leading to kidney injury.
  • Autophagy plays a critical role in cellular homeostasis and response to metabolic stress.

Purpose of the Study:

  • To investigate the activation of autophagy in late-stage diabetic nephropathy (DN) in mice.
  • To determine the association between autophagy and metabolic/inflammatory disturbances in DN.

Main Methods:

  • Comparison of control (db/m) and diabetic nephropathy (db/db) mice over 7 months.
  • Measurement of biochemical indices and kidney tissue analysis.
  • Detection of autophagy markers (LC3-I/II, P62) and related signaling pathways (mTOR, AMPK, SIRT1, HMGB1, IRF3).

Main Results:

  • Autophagy was significantly activated in late-stage DN mice, evidenced by increased LC3-I/II and decreased P62.
  • Key nutrient-sensing pathways (AMPK, SIRT1) and inflammatory markers (HMGB1, IRF3) were upregulated.
  • Mechanistic target of rapamycin (mTOR), a nutrient-sensing regulator, was highly expressed.

Conclusions:

  • Autophagy activation in late-stage DN is linked to metabolic and inflammatory pathway dysregulation.
  • The findings suggest a role for autophagy in the pathogenesis of diabetic nephropathy.
  • Interference with AMPK, SIRT1, HMGB1, and IRF3 signaling pathways by autophagy warrants further investigation.
Keywords:
AutophagyDiabetic nephropathyInflammatory pathwayNutrient-sensing pathway

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