Dynamic cellular changes in acute kidney injury caused by different ischemia time

• Published in: iScience 2023-05, Vol.26 (5), p.106646-106646, Article 106646
• Main Authors: Shan, Dan, Wang, Yin-Ying, Chang, Yuan, Cui, Hao, Tao, Menghao, Sheng, Yixuan, Kang, Hongen, Jia, Peilin, Song, Jiangping
• Format: Article
• Language: English
• Subjects: Disease; Metabolomics; Model organism; Transcriptomics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106646

Ischemia reperfusion injury (IRI), often related to surgical procedures, is one of the important causes of acute kidney injury (AKI). To decipher the dynamic process of AKI caused by IRI (with prolonged ischemia phase), we performed single-cell RNA sequencing (scRNA-seq) of clinically relevant IRI murine model with different ischemic intervals. We discovered that Slc5a2hi proximal tubular cells were susceptible to AKI and highly expressed neutral amino acid transporter gene Slc6a19, which was dramatically decreased over the time course. With the usage of mass spectrometry–based metabolomic analysis, we detected that the level of neutral amino acid isoleucine dropped off in AKI mouse plasma metabolites. And the reduction of plasma isoleucine was also verified in patients with cardiac surgery–associated acute kidney injury (CSA-AKI). The findings advanced the understanding of dynamic process of AKI and introduced reduction of isoleucine as a potential biomarker for CSA-AKI. [Display omitted] •Injured renal cells and neutrophils increased gradually under ischemic injury•Transporter Slc6a19 was downregulated in proximal tubular cells during AKI•Decrease of plasma isoleucine might be a biomarker for acute kidney injury Disease; Metabolomics; Transcriptomics; Model organism