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MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease

Author

Listed:
  • Hisakatsu Sone

    (Augusta University)

  • Tae Jin Lee

    (Augusta University)

  • Byung Rho Lee

    (Augusta University)

  • Dan Heo

    (Augusta University)

  • Sekyung Oh

    (Catholic Kwandong University College of Medicine)

  • Sang-Ho Kwon

    (Augusta University)

Abstract

Chronic kidney disease can develop from kidney injury incident to chemotherapy with cisplatin, which complicates the prognosis of cancer patients. MicroRNAs regulate gene expression by pairing with specific sets of messenger RNAs. Therefore, elucidating direct physical interactions between microRNAs and their target messenger RNAs can help decipher crucial biological processes associated with cisplatin-induced kidney injury. Through intermolecular ligation and transcriptome-wide sequencing, we here identify direct pairs of microRNAs and their target messenger RNAs in the kidney of male mice injured by cisplatin. We find that a group of cisplatin-induced microRNAs can target select messenger RNAs that affect the mitochondrial metabolic pathways in the injured kidney. Specifically, a cisplatin-induced microRNA, miR-429-3p, suppresses the pathway that catabolizes branched-chain amino acids in the proximal tubule, leading to cell death dependent on lipid peroxidation, called ferroptosis. Identification of miRNA-429-3p-mediated ferroptosis stimulation suggests therapeutic potential for modulating the branched-chain amino acid pathway in ameliorating cisplatin-induced kidney injury.

Suggested Citation

  • Hisakatsu Sone & Tae Jin Lee & Byung Rho Lee & Dan Heo & Sekyung Oh & Sang-Ho Kwon, 2023. "MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43529-z
    DOI: 10.1038/s41467-023-43529-z
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    1. Eric L. Nostrand & Peter Freese & Gabriel A. Pratt & Xiaofeng Wang & Xintao Wei & Rui Xiao & Steven M. Blue & Jia-Yu Chen & Neal A. L. Cody & Daniel Dominguez & Sara Olson & Balaji Sundararaman & Liju, 2020. "A large-scale binding and functional map of human RNA-binding proteins," Nature, Nature, vol. 583(7818), pages 711-719, July.
    2. Froukje Vanweert & Michael Neinast & Edmundo Erazo Tapia & Tineke Weijer & Joris Hoeks & Vera B. Schrauwen-Hinderling & Megan C. Blair & Marc R. Bornstein & Matthijs K. C. Hesselink & Patrick Schrauwe, 2022. "A randomized placebo-controlled clinical trial for pharmacological activation of BCAA catabolism in patients with type 2 diabetes," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
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