MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43529-z |
| _version_ | 1797414678469541888 |
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| author | Hisakatsu Sone Tae Jin Lee Byung Rho Lee Dan Heo Sekyung Oh Sang-Ho Kwon |
| author_facet | Hisakatsu Sone Tae Jin Lee Byung Rho Lee Dan Heo Sekyung Oh Sang-Ho Kwon |
| author_sort | Hisakatsu Sone |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T05:37:03Z |
| format | Article |
| id | doaj.art-b4c0c6ee54a846d494293481863c511a |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T05:37:03Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-b4c0c6ee54a846d494293481863c511a2023-12-03T12:27:57ZengNature PortfolioNature Communications2041-17232023-11-0114111410.1038/s41467-023-43529-zMicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney diseaseHisakatsu Sone0Tae Jin Lee1Byung Rho Lee2Dan Heo3Sekyung Oh4Sang-Ho Kwon5Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta UniversityCenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta UniversityDepartment of Cellular Biology and Anatomy, Medical College of Georgia, Augusta UniversityDepartment of Cellular Biology and Anatomy, Medical College of Georgia, Augusta UniversityDepartment of Medical Science, Catholic Kwandong University College of MedicineDepartment of Cellular Biology and Anatomy, Medical College of Georgia, Augusta UniversityAbstract 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.https://doi.org/10.1038/s41467-023-43529-z |
| spellingShingle | Hisakatsu Sone Tae Jin Lee Byung Rho Lee Dan Heo Sekyung Oh Sang-Ho Kwon MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease Nature Communications |
| title | MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease |
| title_full | MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease |
| title_fullStr | MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease |
| title_full_unstemmed | MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease |
| title_short | MicroRNA-mediated attenuation of branched-chain amino acid catabolism promotes ferroptosis in chronic kidney disease |
| title_sort | microrna mediated attenuation of branched chain amino acid catabolism promotes ferroptosis in chronic kidney disease |
| url | https://doi.org/10.1038/s41467-023-43529-z |
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