Inflammation primes the murine kidney for recovery by activating AZIN1 adenosine-to-inosine editing.

Autor:	Heruye SH; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA., Myslinski J; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA., Zeng C; Faculty of Science and Engineering, Waseda University, Tokyo, Japan., Zollman A; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA., Makino S; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA., Nanamatsu A; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA., Mir Q; Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, Indiana, USA., Janga SC; Luddy School of Informatics, Computing, and Engineering, Indiana University, Indianapolis, Indiana, USA., Doud EH; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA., Eadon MT; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA., Maier B; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA., Hamada M; Faculty of Science and Engineering, Waseda University, Tokyo, Japan.; AIST-Waseda University Computational Bio Big-Data Open Innovation Laboratory, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.; Graduate School of Medicine, Nippon Medical School, Tokyo, Japan., Tran TM; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana, USA., Dagher PC; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA., Hato T; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.; Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana, USA.; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Jazyk:	angličtina
Zdroj:	The Journal of clinical investigation [J Clin Invest] 2024 Sep 03; Vol. 134 (17). Date of Electronic Publication: 2024 Sep 03.
DOI:	10.1172/JCI180117
Abstrakt:	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.
Databáze:	MEDLINE
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