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Circadian clock gene BMAL1 reduces urinary calcium oxalate stones formation by regulating NRF2/HO-1 pathway

Jiahao Wang1, Yunjin Bai1, Shan Yin1

  • 1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.

Life Sciences
|December 5, 2020
PubMed

Insights

The circadian rhythm gene BMAL1 regulates the NRF2/HO-1 pathway, reducing oxidative stress and calcium oxalate stone formation. Maintaining normal biological rhythms may prevent stone recurrence.

Area of Science:

  • Nephrology
  • Chronobiology
  • Molecular Biology

Background:

  • Calcium oxalate stones are linked to oxalate metabolism and oxidative stress.
  • Biological rhythms are crucial for maintaining organismal homeostasis.
  • The NRF2/HO-1 pathway combats oxidative stress injury.

Purpose of the Study:

  • To investigate if the circadian gene BMAL1 regulates the NRF2/HO-1 pathway.
  • To determine BMAL1's role in reducing calcium oxalate stone formation.

Main Methods:

  • In vitro experiments with oxalate-induced damage.
  • Overexpression of BMAL1 in cell cultures.
  • Analysis of BMAL1 in a hyperoxaluric animal model.
  • BMAL1 expression and SNP analysis in human patient blood samples.

Main Results:

  • NRF2/HO-1 activation reduced oxalate damage and stone formation, increasing BMAL1 expression.
  • BMAL1 overexpression activated NRF2/HO-1, decreasing oxidative damage.
  • BMAL1 levels were reduced in hyperoxaluric models; NRF2/HO-1 activation decreased stone production.
  • BMAL1 expression and SNPs correlated with calcium oxalate stones in patients.

Conclusions:

  • BMAL1 regulates the NRF2/HO-1 antioxidant pathway.
  • BMAL1 plays a role in preventing calcium oxalate stone formation.
  • Maintaining circadian rhythm and targeting BMAL1/NRF2/HO-1 pathways offers new therapeutic strategies for urinary calculi.
Keywords:
BMAL1CalculusHyperoxaluriaNRF2Oxidative stress

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