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Updated: Jun 25, 2025

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The Spermine Oxidase/Spermine Axis Coordinates ATG5-Mediated Autophagy to Orchestrate Renal Senescence and Fibrosis

Dan Luo1,2, Xiaohui Lu1, Hongyu Li1

  • 1Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, NHC Key Laboratory of Clinical Nephrology, Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, Guangdong, 510080, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|May 22, 2024
PubMed

Insights

Spermine oxidase (SMOX) is elevated in fibrotic kidneys, reducing spermine levels. Targeting this axis improves kidney function by enhancing autophagy and reducing senescence, offering a novel therapeutic strategy for renal fibrosis.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biochemistry

Background:

  • Decreased plasma spermine levels correlate with kidney dysfunction, but its role in kidney disease is unclear.
  • Spermine oxidase (SMOX), involved in polyamine metabolism, is investigated for its role in renal fibrosis.

Purpose of the Study:

  • To investigate the role of spermine oxidase (SMOX) in kidney fibrosis.
  • To explore the therapeutic potential of the SMOX/spermine axis in renal fibrosis.

Main Methods:

  • Assessed SMOX expression in human and mouse fibrotic kidneys.
  • Supplemented with exogenous spermine and utilized genetically deficient SMOX mice.
  • Investigated the interaction between ATG5 and SMOX in fibrotic conditions.

Main Results:

  • SMOX is induced in tubular epithelium of fibrotic kidneys, correlating with fibrosis and kidney function decline.
  • Exogenous spermine or SMOX deficiency improved autophagy, reduced senescence, and attenuated kidney fibrosis.
  • Downregulation of autophagy component ATG5 enhanced SMOX expression and reduced spermine levels.

Conclusions:

  • The SMOX/spermine axis plays a critical role in renal fibrosis.
  • Modulating this axis, potentially by enhancing spermine levels or inhibiting SMOX, could be a novel therapeutic strategy for kidney disease.
  • The findings suggest a link between autophagy, senescence, and the SMOX/spermine pathway in the context of renal fibrosis.
Keywords:
SMOXautophagycell senescencerenal fibrosisspermine

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