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Development of a Noninvasive KIM-1-Based Live-Imaging Technique in the Context of a Drug-Induced Kidney-Injury Mouse Model

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posted on 20.01.2021, 11:13 by Tae-Jun Kwon, Eunseo Jang, Da-Sol Lee, Md. Enamul Haque, Rang-Woon Park, Byungheon Lee, Sang Bong Lee, Dongkyu Kim, Yong-Hyun Jeon, Kil-Soo Kim, Sang Kyoon Kim
The development of reliable methods to diagnose acute kidney injury is essential to allow the adoption of early therapeutic interventions and evaluate their effectiveness. Based on the fact that kidney injury molecule-1 (KIM-1) expression levels in kidneys are markedly upregulated early after a damage event, here we developed a noninvasive KIM-1-based molecular imaging technique to detect kidney injury. First, we took advantage of a phage-display platform to select small peptides demonstrating a specific high binding affinity to KIM-1. The promising candidate was conjugated with fluorescent probes, and its imaging potential was validated in vitro and in vivo. This peptide, with the sequence CNRRRA, not only showed a high imaging potential in vitro, allowing a strong detection of KIM-1 expressing cells by microscopy and flow cytometry but also generated a strong kidney-specific signal in live-imaging in vivo experiments in the context of a drug-induced kidney-injury mouse model. Our data overall suggest that the CNRRRA peptide is a promising probe to use in the context of in vivo imaging for the detection of KIM-1 overexpression in damaged kidneys.

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