{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1390306805490277248.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.2131/jts.51.75"}},{"identifier":{"@type":"URI","@value":"https://www.jstage.jst.go.jp/article/jts/51/1/51_75/_pdf"}}],"dc:title":[{"@language":"en","@value":"Predicting nucleic acid drug-induced nephrotoxicity using a 3D human renal proximal tubule spheroid model"}],"dc:language":"en","description":[{"type":"abstract","notation":[{"@language":"en","@value":"<p>Nucleic acid drugs hold considerable promise; however, their toxicological profiles are often difficult to assess in animal models. Clinical studies have reported adverse effects, including thrombocytopenia, complement activation, hepatotoxicity, and nephrotoxicity. While human cell-based models for hepatotoxicity are advancing, nephrotoxicity assessment remains limited by the scarcity of physiologically relevant kidney cells. In this study, a three-dimensional spheroid model of human primary renal proximal tubule epithelial cells (3D-RPTEC, Nikkiso) was employed to evaluate the nephrotoxicity of nucleic acid drugs. Proteomic profiling revealed enhanced expression of drug transporters and endocytic machinery in 3D-RPTEC compared with two-dimensional cultures. Lipofection enabled efficient intracellular delivery of nucleic acids. Toxicity was assessed using ATP quantification, biomarker analysis (LDH, KIM-1, NGAL), and high-content analysis (HCA). Significant ATP depletion was observed only after prolonged exposure to SPC5001, a nephrotoxic antisense oligonucleotide. In contrast, biomarker expression and HCA facilitated early detection of compound-specific toxicity and implicated endoplasmic reticulum and mitochondrial stress as underlying mechanisms. These findings establish 3D-RPTEC as a sensitive and physiologically relevant platform for predicting the nephrotoxic potential of nucleic acid drugs.</p>"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410306805490277254","@type":"Researcher","foaf:name":[{"@language":"en","@value":"Morimura Kaoru"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Bio Business Promotion Department, Medical Division, NIKKISO Co., Ltd."},{"@language":"en","@value":"Department of Systems Bioscience, Graduate School of Systems Life Sciences, Kyushu University"}]},{"@id":"https://cir.nii.ac.jp/crid/1410306805490277248","@type":"Researcher","foaf:name":[{"@language":"en","@value":"Takahashi Etsushi"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Bio Business Promotion Department, Medical Division, NIKKISO Co., Ltd."}]},{"@id":"https://cir.nii.ac.jp/crid/1410306805490277253","@type":"Researcher","foaf:name":[{"@language":"en","@value":"Maeda Hayata"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Bio Business Promotion Department, Medical Division, NIKKISO Co., Ltd."}]},{"@id":"https://cir.nii.ac.jp/crid/1410306805490277252","@type":"Researcher","foaf:name":[{"@language":"en","@value":"Nishioka Yukiko"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Bio Business Promotion Department, Medical Division, NIKKISO Co., Ltd."}]},{"@id":"https://cir.nii.ac.jp/crid/1410306805490277251","@type":"Researcher","foaf:name":[{"@language":"en","@value":"Araki Ayano"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Bio Business Promotion Department, Medical Division, NIKKISO Co., Ltd."}]},{"@id":"https://cir.nii.ac.jp/crid/1410306805490277249","@type":"Researcher","foaf:name":[{"@language":"en","@value":"Mizumoto Hiroshi"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Systems Bioscience, Graduate School of Systems Life Sciences, Kyushu University"}]},{"@id":"https://cir.nii.ac.jp/crid/1410306805490277250","@type":"Researcher","foaf:name":[{"@language":"en","@value":"Jimbo Yoichi"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Bio Business Promotion Department, Medical Division, NIKKISO Co., Ltd."}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"03881350"},{"@type":"LISSN","@value":"03881350"},{"@type":"EISSN","@value":"18803989"}],"prism:publicationName":[{"@language":"en","@value":"The Journal of Toxicological Sciences"},{"@language":"ja","@value":"Ｔｈｅ　Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃａｌ　Ｓｃｉｅｎｃｅｓ"},{"@language":"en","@value":"J. Toxicol. Sci."}],"dc:publisher":[{"@language":"en","@value":"The Japanese Society of Toxicology"},{"@language":"ja","@value":"一般社団法人　日本毒性学会"}],"prism:publicationDate":"2026","prism:volume":"51","prism:number":"1","prism:startingPage":"75","prism:endingPage":"87"},"reviewed":"false","url":[{"@id":"https://www.jstage.jst.go.jp/article/jts/51/1/51_75/_pdf"}],"availableAt":"2026","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Nucleic%20acid%20drugs","dc:title":"Nucleic acid drugs"},{"@id":"https://cir.nii.ac.jp/all?q=Nephrotoxicity","dc:title":"Nephrotoxicity"},{"@id":"https://cir.nii.ac.jp/all?q=3D%20kidney%20spheroids","dc:title":"3D kidney spheroids"},{"@id":"https://cir.nii.ac.jp/all?q=Drug-induced%20toxicity","dc:title":"Drug-induced toxicity"},{"@id":"https://cir.nii.ac.jp/all?q=Renal%20proximal%20tubule%20epithelial%20cells","dc:title":"Renal proximal tubule epithelial cells"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004233989008768","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Unbiased Quantitation of Escherichia coli Membrane Proteome Using Phase Transfer Surfactants"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011145006473728","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Current nonclinical testing paradigm enables safe entry to First-In-Human clinical trials: The IQ consortium nonclinical to clinical translational database"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011145296781440","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"HK-2: An immortalized proximal tubule epithelial cell line from normal adult human kidney"}]},{"@id":"https://cir.nii.ac.jp/crid/1360013265884682496","@type":"Article","resourceType":"学術雑誌論文(journal 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