Retinol Binding Protein 4 Is a Marker for Proteinuria in Humans and Zebrafish
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Le résumé fourni par la source
Background: A clinical hallmark of glomerular kidney diseases is proteinuria. In humans, proteinuria is described as the urinary albumin-creatine-ratio. The zebrafish is a widely used model in kidney research. However, up to date proteinuria detection in zebrafish requires transgenic lines, because the zebrafish does not possess an albumin orthologue. Although allowing for proteinuria-related kidney research in zebrafish, these transgenic lines may possess altered physiology and lack direct translational potential to human health. Methods: We performed proteomics on fish water samples of zebrafish larvae with a described glomerular damage phenotype (magi2acl604). We designed and 3D-printed a custom dot blot plate to subject water samples of zebrafish larvae individually housed for 24 hours on a PVDF membrane. Assessment of proteinuria was performed by detecting Rbp4 on the membrane. To induce glomerular damage, different transgenic lines, a chemical induction model and somatic CRISPR knock-out models were used. Additionally, a fluorescent eye assay using the transgenic line Tg(lfab:VDBP-eGFP) was performed to compare the performance of the novel assay to a standard zebrafish proteinuria assay. Results: Using a proteomics approach, we found high abundance of rbp4 in fish water of edema fish compared to control fish. It has been shown before that RBP4 is proteinuria marker in humans as well. Based on that, we developed a dot blot-based assay where fish water is used to quantify proteinuria in individually housed zebrafish larvae by immunodetection of Rbp4. Using four different established models to induce proteinuria in zebrafish, we validated the dot blot-based assay. Conclusion: We developed a novel proteinuria assay in zebrafish based on the endogenous orthologue of a known human proteinuria marker. This assay allows for individual proteinuria assessment, independent of transgenic zebrafish lines and with a higher physiological relevance. Thereby, we established a novel translational assay that is useful for drug discovery as it is scalable and suitable for high-throughput procedures. Funding: Other NIH Support - P20GM103423 and P20GM104318, Government Support – Non-U.S.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Retinol Binding Protein 4 Is a Marker for Proteinuria in Humans and Zebrafish
- Date Crossref
- 01/10/2024
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Friedrich-Alexander-Universität Erlangen-Nürnberg pays non établi dans la noticeUniversité ou école supérieure
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Mount Desert Island Biological Laboratory pays non établi dans la noticeOrganisation à but non lucratif
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Universitätsklinikum Erlangen pays non établi dans la noticeÉtablissement de santé
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Boston Children's Hospital Department of Pediatrics pays non établi dans la noticeÉtablissement de santé
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Harvard University pays non établi dans la noticeUniversité ou école supérieure
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Aarhus University pays non établi dans la noticeUniversité ou école supérieure
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University Hospital Erlangen Department of Nephrology and Hypertension pays non établi dans la noticeUniversité ou école supérieure
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Aarhus Universitet Institut for Biomedicin pays non établi dans la noticeUniversité ou école supérieure
Friedrich-Alexander-Universität Erlangen-Nürnberg, Mount Desert Island Biological Laboratory et Universitätsklinikum Erlangen, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.