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Updated: Oct 23, 2025

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

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Cannabinoid receptor 2 plays a central role in renal tubular mitochondrial dysfunction and kidney ageing

Shan Zhou1, Xian Ling1, Ping Meng2

  • 1State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Journal of Cellular and Molecular Medicine
|August 20, 2021
PubMed

Insights

Cannabinoid receptor 2 (CB2) activation drives kidney aging by impairing mitochondria and promoting cell senescence. Blocking CB2 or its associated beta-catenin signaling protects against kidney dysfunction and fibrosis.

Area of Science:

  • Nephrology
  • Cell Biology
  • Aging Research

Background:

  • Mitochondrial dysfunction is crucial in renal tubular cell senescence and kidney aging.
  • The precise mechanisms linking mitochondrial dysfunction to kidney aging remain unclear.
  • Cannabinoid receptor 2 (CB2) is upregulated in chronic kidney disease and kidney aging, but its role in tubular mitochondrial dysfunction is unknown.

Purpose of the Study:

  • To investigate the role of Cannabinoid receptor 2 (CB2) in renal tubular mitochondrial dysfunction and kidney aging.
  • To elucidate the underlying mechanisms involving CB2 activation and beta-catenin signaling.

Main Methods:

  • Examined CB2 expression in aging and d-galactose-induced accelerated aging mouse models.
  • Utilized CB2 gene deletion and overexpression in mouse models and cultured human renal proximal tubular cells.
  • Assessed mitochondrial mass, ATP production, PGC-1α levels, and beta-catenin signaling.
  • Investigated the effects of CB2 agonist (AM1241) and beta-catenin blocker (ICG-001).

Main Results:

  • CB2 was upregulated in aging kidneys, correlating with decreased mitochondrial mass.
  • CB2 deletion in aging mice inhibited beta-catenin activation, restored mitochondrial integrity and ATP production, and reduced senescence and fibrosis.
  • CB2 overexpression/activation induced mitochondrial dysfunction, decreased mitochondria-related proteins (e.g., PGC-1α), and triggered senescence in human renal cells.
  • Beta-catenin signaling blockade prevented CB2-induced mitochondrial dysfunction and senescence.

Conclusions:

  • CB2 plays a central role in renal tubular mitochondrial dysfunction and kidney aging.
  • CB2 activation contributes to kidney aging and fibrosis, potentially through the beta-catenin signaling pathway.
  • Targeting CB2 or beta-catenin signaling may offer therapeutic strategies for kidney aging and related diseases.
Keywords:
CB2kidney ageingmitochondrial dysfunctiontubular cellβ-catenin

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