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

Dan Shan; Yin-Ying Wang; Yuan Chang; Hao Cui; Menghao Tao; Yixuan Sheng; Hongen Kang; Peilin Jia; Jiangping Song

doi:10.1016/j.isci.2023.106646

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

iScience. 2023 Apr 11;26(5):106646. doi: 10.1016/j.isci.2023.106646. eCollection 2023 May 19.

Authors

Dan Shan^{1

2}, Yin-Ying Wang³, Yuan Chang^{1

2}, Hao Cui^{1

2}, Menghao Tao^{1

2}, Yixuan Sheng^{1

4}, Hongen Kang^{3

5}, Peilin Jia^{3

5}, Jiangping Song^{1

2}

Affiliations

¹ Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Fuwai Hospital, National Centre for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
² The Cardiomyopathy Research Group at Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
³ CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing 100101, China.
⁴ Department of Cardiovascular Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510000, China.
⁵ University of Chinese Academy of Sciences, Beijing 100049, China.

Abstract

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 Slc5a2^hi 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.

Keywords: Disease; Metabolomics; Model organism; Transcriptomics.