Identification of mechanistic CKD biomarkers in a rat SNx kidney fibrosis model by transcriptomics and proteomics detectable in biofluids
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...
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Nature Portfolio
2025-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-93894-6 |
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| author | Karin Barnouin Elisa Tonoli Clare Coveney John Atkinson Margarida Sancho Andrew Skelton David J. Boocock Linghong Huang Joseph Shephard Timothy S. Johnson Elisabetta A. M. Verderio Breda Twomey |
| author_facet | Karin Barnouin Elisa Tonoli Clare Coveney John Atkinson Margarida Sancho Andrew Skelton David J. Boocock Linghong Huang Joseph Shephard Timothy S. Johnson Elisabetta A. M. Verderio Breda Twomey |
| author_sort | Karin Barnouin |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b9754673fd9d4286bdb4fe79ee78c9f5 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-b9754673fd9d4286bdb4fe79ee78c9f52025-08-20T01:52:55ZengNature PortfolioScientific Reports2045-23222025-04-0115111310.1038/s41598-025-93894-6Identification of mechanistic CKD biomarkers in a rat SNx kidney fibrosis model by transcriptomics and proteomics detectable in biofluidsKarin Barnouin0Elisa Tonoli1Clare Coveney2John Atkinson3Margarida Sancho4Andrew Skelton5David J. Boocock6Linghong Huang7Joseph Shephard8Timothy S. Johnson9Elisabetta A. M. Verderio10Breda Twomey11UCB PharmaSchool of Science and Technology, Centre for Systems Health and Integrated Metabolic Research (SHiMR), Nottingham Trent UniversityJohn Van Geest Cancer Research Centre, Nottingham Trent UniversityUCB PharmaUCB PharmaUCB PharmaJohn Van Geest Cancer Research Centre, Nottingham Trent UniversityUCB PharmaUCB PharmaUCB PharmaSchool of Science and Technology, Centre for Systems Health and Integrated Metabolic Research (SHiMR), Nottingham Trent UniversityUCB PharmaAbstract 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.https://doi.org/10.1038/s41598-025-93894-6 |
| spellingShingle | Karin Barnouin Elisa Tonoli Clare Coveney John Atkinson Margarida Sancho Andrew Skelton David J. Boocock Linghong Huang Joseph Shephard Timothy S. Johnson Elisabetta A. M. Verderio Breda Twomey Identification of mechanistic CKD biomarkers in a rat SNx kidney fibrosis model by transcriptomics and proteomics detectable in biofluids Scientific Reports |
| title | Identification of mechanistic CKD biomarkers in a rat SNx kidney fibrosis model by transcriptomics and proteomics detectable in biofluids |
| title_full | Identification of mechanistic CKD biomarkers in a rat SNx kidney fibrosis model by transcriptomics and proteomics detectable in biofluids |
| title_fullStr | Identification of mechanistic CKD biomarkers in a rat SNx kidney fibrosis model by transcriptomics and proteomics detectable in biofluids |
| title_full_unstemmed | Identification of mechanistic CKD biomarkers in a rat SNx kidney fibrosis model by transcriptomics and proteomics detectable in biofluids |
| title_short | Identification of mechanistic CKD biomarkers in a rat SNx kidney fibrosis model by transcriptomics and proteomics detectable in biofluids |
| title_sort | identification of mechanistic ckd biomarkers in a rat snx kidney fibrosis model by transcriptomics and proteomics detectable in biofluids |
| url | https://doi.org/10.1038/s41598-025-93894-6 |
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