Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, 80 Cheombok-ro, Dong-gu, Daegu 41061, Korea.
Department of Biochemistry and Cell Biology, BK21 Plus KNU Biomedical Convergence Program, CMRI, School of Medicine, Kyungpook National University, Daegu 41566, Korea.
ACS Appl Bio Mater. 2021 Feb 15;4(2):1508-1514. doi: 10.1021/acsabm.0c01392. Epub 2021 Jan 20.
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 and . This peptide, with the sequence CNRRRA, not only showed a high imaging potential , 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 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 imaging for the detection of KIM-1 overexpression in damaged kidneys.
开发可靠的方法来诊断急性肾损伤对于早期治疗干预的采用和评估其疗效至关重要。基于肾脏损伤分子-1（KIM-1）在损伤事件后早期表达水平明显上调的事实，我们在此开发了一种基于 KIM-1 的非侵入性分子成像技术来检测肾损伤。首先，我们利用噬菌体展示平台来筛选对 KIM-1 具有特异性高结合亲和力的小肽。将有前途的候选肽与荧光探针缀合，并验证了其成像潜力。该肽的序列为 CNRRRA，不仅表现出高的成像潜力，通过显微镜和流式细胞术可以强烈检测到表达 KIM-1 的细胞，而且在药物诱导的肾损伤小鼠模型的活体成像实验中产生了强烈的肾脏特异性信号。我们的数据总体表明，CNRRRA 肽是一种很有前途的探针，可用于 成像以检测受损肾脏中 KIM-1 的过表达。
