Advertisement
ResearchIn-Press PreviewNephrology
Open Access | 10.1172/JCI180117
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by Heruye, S. in: JCI | PubMed | Google Scholar
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by
Myslinski, J.
in:
JCI
|
PubMed
|
Google Scholar
|
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by Zeng, C. in: JCI | PubMed | Google Scholar
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by Zollman, A. in: JCI | PubMed | Google Scholar
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by Makino, S. in: JCI | PubMed | Google Scholar
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by
Nanamatsu, A.
in:
JCI
|
PubMed
|
Google Scholar
|
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by Mir, Q. in: JCI | PubMed | Google Scholar
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by
Janga, S.
in:
JCI
|
PubMed
|
Google Scholar
|
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by Doud, E. in: JCI | PubMed | Google Scholar
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by
Eadon, M.
in:
JCI
|
PubMed
|
Google Scholar
|
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by Maier, B. in: JCI | PubMed | Google Scholar
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by Hamada, M. in: JCI | PubMed | Google Scholar
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by Tran, T. in: JCI | PubMed | Google Scholar
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by Dagher, P. in: JCI | PubMed | Google Scholar
1Department of Medicine, Indiana University School of Medicine, Indianapolis, United States of America
2Faculty of Science and Engineering, Waseda University, Tokyo, Japan
3Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, United States of America
4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United States of America
Find articles by
Hato, T.
in:
JCI
|
PubMed
|
Google Scholar
|
Published July 2, 2024 - More info
The progression of kidney disease varies among individuals, but a general methodology to quantify disease timelines is lacking. Particularly challenging is the task of determining the potential for recovery from acute kidney injury following various insults. Here, we report that quantitation of post-transcriptional adenosine-to-inosine (A-to-I) RNA editing offers a distinct genome-wide signature, enabling the delineation of disease trajectories in the kidney. A well-defined murine model of endotoxemia permitted the identification of the origin and extent of A-to-I editing, along with temporally discrete signatures of double-stranded RNA stress and Adenosine Deaminase isoform switching. We found that A-to-I editing of Antizyme Inhibitor 1 (AZIN1), a positive regulator of polyamine biosynthesis, serves as a particularly useful temporal landmark during endotoxemia. Our data indicate that AZIN1 A-to-I editing, triggered by preceding inflammation, primes the kidney and activates endogenous recovery mechanisms. By comparing genetically modified human cell lines and mice locked in either A-to-I edited or uneditable states, we uncovered that AZIN1 A-to-I editing not only enhances polyamine biosynthesis but also engages glycolysis and nicotinamide biosynthesis to drive the recovery phenotype. Our findings implicate that quantifying AZIN1 A-to-I editing could potentially identify individuals who have transitioned to an endogenous recovery phase. This phase would reflect their past inflammation and indicate their potential for future recovery.