Identification of mechanistic CKD biomarkers in a rat SNx kidney fibrosis model by transcriptomics and proteomics detectable in biofluids

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Barnouin, K, Tonoli, E ORCID: https://orcid.org/0000-0001-9774-1048, Coveney, C ORCID: https://orcid.org/0000-0001-7047-6408, Atkinson, J, Sancho, M, Skelton, A, Boocock, DJ ORCID: https://orcid.org/0000-0002-7333-3549, Huang, L, Shephard, J, Johnson, TS, Verderio, EAM ORCID: https://orcid.org/0000-0001-9153-8997 and Twomey, B, 2025. Identification of mechanistic CKD biomarkers in a rat SNx kidney fibrosis model by transcriptomics and proteomics detectable in biofluids. Scientific Reports, 15: 11200. ISSN 2045-2322

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Official URL: https://doi.org/10.1038/s41598-025-93894-6

Abstract

The rat sub-total nephrectomy (SNx) is a functional model of general chronic kidney disease (CKD) where the main pathological driver is glomerular hypertension representative of several subtypes of CKD. Comprehensive transcriptomics and proteomics analyses on the SNx rats were performed to identify biomarkers in plasma or urine that correlate with kidney disease and functional kidney loss. Kidneys were subjected to collagen I and III staining for fibrosis scoring, SWATH-MS proteomics and bulk RNA-sequencing transcriptomics, with SWATH-MS also performed on plasma and urine. Differential expression analysis demonstrated significant dysregulation of genes and proteins involved in fibrosis, metabolism, and immune response in the SNx rats compared to controls. Gene ontology analysis of the intersecting genes and proteins from both studies demonstrated common biology between animal cohorts that reached the predefined kidney disease thresholds (serum creatinine > two-fold or proteinuria > three-fold increase over sham-operated). Thirteen significantly differential molecules were detected with consistent directional changes in both omics datasets. These molecules were detected independently in kidney (both RNA and protein) and urine (protein only), but not in plasma. Bioinformatics analysis enabled the identification of mechanistic CKD biomarkers including lumican and collagen alpha-1(III) chain, whose co-expression has previously been both implicated in fibrosis and detected in urine in CKD patients.

Item Type:	Journal article
Publication Title:	Scientific Reports
Creators:	Barnouin, K., Tonoli, E., Coveney, C., Atkinson, J., Sancho, M., Skelton, A., Boocock, D.J., Huang, L., Shephard, J., Johnson, T.S., Verderio, E.A.M. and Twomey, B.
Publisher:	Nature Research (part of Springer Nature)
Date:	2 April 2025
Volume:	15
ISSN:	2045-2322
Identifiers:	Number Type 10.1038/s41598-025-93894-6 DOI 2420664 Other
Rights:	© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Borcherds
Date Added:	02 Apr 2025 12:22
Last Modified:	02 Apr 2025 12:22
URI:	https://irep.ntu.ac.uk/id/eprint/53350