Increased Renal Versican Expression Is Associated with Progression of Chronic Kidney Disease
| Autor: | Bernd Mayer, Michael A. Rudnicki, Judith Sunzenauer, Hannes Neuwirt, Carlamaria Zoja, Johannes Leierer, Susanne Eder, Paul Perco, Susie Jane Noppert, Gert Mayer, Alexander R. Rosenkranz, Gerhard A. Müller, Kathrin Eller |
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| Přispěvatelé: | Dussaule, Jean-Claude |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Pathology
Biopsy lcsh:Medicine Kidney Biochemistry Transcriptomes Diabetic nephropathy Kidney Tubules Proximal chemistry.chemical_compound Mice 0302 clinical medicine Versicans Risk Factors Molecular Cell Biology Chronic Kidney Disease RNA Isoforms lcsh:Science 0303 health sciences Extracellular Matrix Proteins Multidisciplinary medicine.diagnostic_test biology Systems Biology Genomics Prognosis 3. Good health Extracellular Matrix medicine.anatomical_structure Nephrology 030220 oncology & carcinogenesis Disease Progression Cytochemistry Versican Medicine Research Article medicine.medical_specialty Renal function Increased Renal Versican Expression Progression Cell Line Transforming Growth Factor beta1 03 medical and health sciences Genome Analysis Tools Diagnostic Medicine medicine Animals Humans Renal Insufficiency Chronic Biology 030304 developmental biology Creatinine business.industry lcsh:R Glomerulosclerosis Proteins Computational Biology Fibroblasts medicine.disease Rats carbohydrates (lipids) Disease Models Animal chemistry Gene Expression Regulation Tubulointerstitial Disease biology.protein lcsh:Q business Biomarkers Kidney disease General Pathology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 9, p e44891 (2012) |
| Popis: | Novel prognostic markers for progression of kidney disease are needed to distinguish patients who might benefit from a more aggressive nephroprotective therapy. Expression of the proteoglycan versican was evaluated in renal transcriptomics profiles and in an independent set of 74 renal biopsies. Versican levels were correlated to histologic damage scores and to renal outcome, and versican expression and regulation was evaluated in vitro. In transcriptomics profiles of renal tissue versican was positively correlated with (i) histological parameters in kidney biopsies, (ii) progressive decline of renal function in proteinuric kidney diseases, and (iii) impaired renal function and histology scores in diabetic nephropathy. In an independent cohort of 74 biopsies of glomerular diseases renal RNA levels of versican isoforms V0 and V1, but not V2 and V3 correlated significantly with creatinine after a mean follow up time of 53 months. Versican isoforms V0 and V1 together with serum creatinine at time of biopsy and the degree of glomerulosclerosis predicted 20% and 24% of the variability of creatinine at follow up, which was significantly more than serum creatinine and histological parameters alone (16%). However, when patients with acute kidney failure at time of biopsy (n = 5) were excluded, the additive predictive value of versican V1 was only marginally higher (35%) than creatinine and glomerulosclerosis alone (34%). Versican isoforms V0 and V1 were primarily expressed in vitro in proximal tubule cells and in fibroblasts. The results in humans were confirmed in three rodent models of kidney disease, in which renal versican expression was significantly upregulated as compared to corresponding controls. These data show for the first time an association of renal versican isoform V0 and V1 expression with progressive renal disease. peerReviewed |
| Databáze: | OpenAIRE |
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