MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease.
MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease.
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microRNA介导的支链氨基酸催化剂的衰减促进慢性肾脏疾病中的铁凋亡
DOI：
10.1038/s41467-023-43529-z
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发表时间：
2023-11-28
影响因子：
16.6
通讯作者：
Kwon, Sang-Ho
中科院分区：
文献类型：
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作者：
Sone, Hisakatsu;Lee, Tae Jin;Lee, Byung Rho;Heo, Dan;Oh, Sekyung;Kwon, Sang-Ho
慢性肾脏疾病可由肾损伤事件发展为顺铂化疗，这使癌症患者的预后复杂化。microRNA通过与特定的信使RNA配对来调节基因表达。因此，阐明microRNA与其靶信使RNA之间的直接物理相互作用可以帮助破译与顺铂诱导的肾损伤相关的关键生物学过程。通过分子间连接和全转录组测序，我们在此鉴定了顺铂损伤的雄性小鼠肾脏中直接成对的microRNA及其靶信使RNA。我们发现一组顺铂诱导的microRNA可以靶向选择影响损伤肾脏线粒体代谢途径的信使RNA。具体而言，顺铂诱导的microRNA，miR-429- 3 p，抑制近端小管中分解代谢支链氨基酸的途径，导致依赖于脂质过氧化的细胞死亡，称为铁凋亡。miRNA-429- 3 p介导的铁凋亡刺激的鉴定表明调节支链氨基酸途径在改善顺铂诱导的肾损伤中的治疗潜力。顺铂是一种化疗药物，可导致长期的肾损伤。作者探索了顺铂损伤肾脏中miRNA：mRNA的相互作用，发现顺铂诱导的miRNA如miR-429- 3 p抑制支链氨基酸的催化，导致刺激铁凋亡细胞死亡。
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. Cisplatin, a chemotherapy drug, can cause long-lasting kidney injury. The authors explore miRNA:mRNA interactions in cisplatin-injured kidneys and find that such a cisplatin inducible miRNA as miR-429-3p suppresses the catabolism of branched-chain amino acids, leading to stimulation of ferroptotic cell death.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
DOI：
10.1152/ajprenal.2000.278.5.f758
发表时间：
2000-05-01
影响因子：
4.2
作者：
Bergin, E;Levine, JS;Lieberthal, W
通讯作者：
Lieberthal, W
影响因子：
81.5
作者：
Kellum, John A.;Romagnani, Paola;Anders, Hans-Joachim
通讯作者：
Anders, Hans-Joachim
影响因子：
1.7
作者：
Kechin, Andrey;Boyarskikh, Uljana;Filipenko, Maxim
通讯作者：
Filipenko, Maxim
影响因子：
16
作者：
通讯作者：
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