• Akinori Aomatsu, Shohei Kaneko, Katsunori Yanai, Hiroki Ishii, Kiyonori Ito, Keiji Hirai, Susumu Ookawara, Yasuma Kobayashi, Masamitsu Sanui, and Yoshiyuki Morishita.
• Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan; Division of Intensive Care Unit, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
• Transl Res. 2022 Jun 1; 244: 1-31.

AbstractThe aim of this study was to identify miRNAs that regulate AKI and develop their applications as diagnostic biomarkers and therapeutic agents. First, kidney tissues from two different AKI mouse models, namely, AKI induced by the administration of lipopolysaccharide (LPS) causing sepsis (LPS-AKI mice) and AKI induced by renal ischemia-reperfusion injury (IRI-AKI mice), were exhaustively screened for their changes of miRNA expression compared with that of control mice by microarray analysis followed by quantitative RT-PCR. The initial profiling newly identified miRNA-5100, whose expression levels significantly decreased in kidneys in both LPS-AKI mice and IRI-AKI mice. Next, the administration of miRNA-5100-mimic conjugated with a nonviral vector, polyethylenimine nanoparticles (PEI-NPs), via the tail vein significantly induced miRNA-5100 overexpression in the kidney and prevented the development of IRI-AKI mice by inhibiting several apoptosis pathways in vivo. Furthermore, serum levels of miRNA-5100 in patients with AKI were identified as significantly lower than those of healthy subjects. ROC analysis showed that the serum expression level of miRNA-5100 can identify AKI (cut-off value 0.14, AUC 0.96, sensitivity 1.00, specificity 0.833, p<0.05). These results suggest that miRNA-5100 regulates AKI and may be useful as a novel diagnostic biomarker and therapeutic target for AKI.Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

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