Involvement of REV-ERBα dysregulation and ferroptosis in aristolochic acid I-induced renal injury

Oct 21, 2021Biochemical pharmacology

REV-ERBα imbalance and iron-dependent cell death linked to kidney damage from aristolochic acid I

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Abstract

REV-ERBα is identified as a regulator of AAI-induced renal injury via promoting ferroptosis.

  • REV-ERBα was upregulated and its target BMAL1 was downregulated in the kidneys of mice with AAI nephropathy.
  • Ferroptosis was enhanced in mice with AAI nephropathy and in kidney cells treated with aristolactam I.
  • Knocking out Rev-erbα made mice less sensitive to AAI-induced ferroptosis and renal injury.
  • Reducing Rev-erbα levels through siRNA or the antagonist SR8278 decreased ferroptosis in kidney cells.
  • Antagonism of REV-ERBα by SR8278 alleviated ferroptosis and renal injury in mice caused by AAI.

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