권상호 (Augusta University Medical College of Georgia) | 한빛사논문 > 한빛사

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Augusta University Medical College of Georgia

Nat. Commun., Nov 28 2023, 14 (1) | https://doi.org/10.1038/s41467-023-43529-z MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease

Hisakatsu Sone ¹, Tae Jin Lee ², Byung Rho Lee ¹, Dan Heo ¹, Sekyung Oh ³, Sang-Ho Kwon ^{4 *}

¹Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
²Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, 30912, USA.
³Department of Medical Science, Catholic Kwandong University College of Medicine, Incheon, 22711, South Korea.
⁴Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.

^*Corresponding author: correspondence to Sang-Ho Kwon

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.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-12-18)
연구진국내+국외 연구진
분야 생명과학 > 세포생물학

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