Dataset Information

Glomerulonephritis-induced changes in kidney gene expression in rats.

ABSTRACT: We investigated a glomerulonephritis (GN) model in rats induced by nephrotoxic serum (NTS) which contains antibodies against the glomerular basement membrane (GBM). The anti-GBM GN model in rats is widely used since its biochemical and histopathological characteristics are similar to crescentic nephritis and Goodpasture's disease in humans (Pusey, 2003[2]). Male Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats were dosed once with 1, 2.5 and 5 ml/kg nephrotoxic serum (NTS) or 1.5 and 5 ml/kg NTS, respectively. GN and tubular damage were observed histopathologically in all treated rats after 14 days. To obtain insight into molecular processes during GN pathogenesis, mRNA expression was investigated in WKY and SD kidneys using Affymetrix's GeneChip Rat genome 230_2.0 arrays (GSE64265). The immunopathological processes during GN are still not fully understood and likely involve both innate and adaptive immunity. In the present study, several hundred mRNAs were found deregulated, which functionally were mostly associated with inflammation and regeneration. The ?-chain of the major histocompatibility complex class II RT1.B (Rt1-Bb) and complement component 6 (C6) were identified as two mRNAs differentially expressed between WKY and SD rat strains which could be related to known different susceptibilities to NTS of different rat strains; both were increased in WKY and decreased in SD rats (Pavkovic et al., 2015 [1]). Increased Rt1-Bb expression in WKY rats could indicate a stronger and more persistent cellular reaction of the adaptive immune system in this strain, in line with findings indicating adaptive immune reactions during GN. The complement cascade is also known to be essential for GN development, especially terminal cascade products like C6.

SUBMITTER: Pavkovic M

PROVIDER: S-EPMC4664719 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Glomerulonephritis-induced changes in kidney gene expression in rats.

Pavkovic Mira M Riefke Björn B Frisk Anna-Lena AL Gröticke Ina I Ellinger-Ziegelbauer Heidrun H

Genomics data 20150818

We investigated a glomerulonephritis (GN) model in rats induced by nephrotoxic serum (NTS) which contains antibodies against the glomerular basement membrane (GBM). The anti-GBM GN model in rats is widely used since its biochemical and histopathological characteristics are similar to crescentic nephritis and Goodpasture's disease in humans (Pusey, 2003[2]). Male Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats were dosed once with 1, 2.5 and 5 ml/kg nephrotoxic serum (NTS) or 1.5 and 5 ml/kg NTS, ...[more]

PMID: 26697341

Similar Datasets

Project description:Diabetes is a complex metabolic disorder and different environmental toxicants including heavy metals have been involved in diabetes induction. Therefore, assessment of the environmental risk factors and heavy metals induced toxicity have become critical for reducing the consequences of metals pollutants. Previously, we reported heavy metals induced nephrotoxicity in non-diabetic and diabetic rats. Here, we extended our analysis by examining the heavy metals induced organs (heart, kidney, liver, pancreas, and spleen) damage in diabetic and non-diabetic Wistar rats using histopathology and quantitative real-time PCR (qRT-PCR). Following the generation of the diabetic rat model, the animals were exposed to heavy metals including lead (Pb), arsenic (As), manganese (Mn) and cadmium (Cd). Both non-diabetic and diabetic rats were exposed to heavy metals for 30 days and subsequently, the heart, kidney, liver, pancreas and spleen tissues were examined. Heavy metal treatment resulted in irregularly arranged myofibrils and vacuolization in the heart tissue of metal treated groups as evident from hematoxylin and eosin (H & E) staining. The kidney tissue of rats treated with heavy metals showed tubular degeneration, fibrosis, hemorrhage, and vacuolation. The liver of the heavy metals treated rats exhibited cellular degeneration and necrosis. The pancreatic tissue of streptozotocin injected untreated and metal treated rats revealed severe degeneration, necrosis, degranulation, shrinkage, and depression in the islets of Langerhans. Increased red pulp area and congestion were observed in the spleen of the metal mixture treated non-diabetic and diabetic rats. In line with the histological data, the qRT-PCR analysis showed downregulated expression of Bcl2 and upregulation of Caspase-3 in non-diabetic and diabetic metal treated rats as compared to the non-diabetic untreated rats. In conclusion, the present study revealed, diabetic rats are more prone to metal alone as well as metal mixture induced organ damage as compared to non-diabetic rats.

Project description:BackgroundThe bacterial endotoxin lipopolysaccharide (LPS) was the classic inducer to establish many inflammatory disease models, especially multiple organ injury. Evidences indicated that the mechanism that causes inflammation response is not just related to cytokine release. The main aim of this study was to better elucidate the possible links between metabolic changes and the pathogenesis of LPS-induced acute liver and kidney in order to understand the mechanisms and screening therapeutic targets for developing early diagnostic strategies and treatments.MethodsAn experimental rat model was established by intraperitoneal injection of 10 mg/kg LPS. An untargeted metabolomics analysis of the serum in the LPS and control groups was carried out using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/QTOF-MS). LPS-induced pathological damage in the lungs, liver, kidneys, and colon was observed, along with changes in biochemical indexes, indicating that there was a severe inflammatory response in many organs after administration of LPS for 8 h. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) showed distinct separation in the serum metabolite profiles between the LPS and control groups, indicating significant changes in endogenous metabolites.ResultsThe untargeted metabolomics analysis showed that there were 127 significantly different serum metabolites and 53 altered pathways after LPS administration, including pathways related to the metabolism of D-glutamine and D-glutamate, taurine and hypotaurine, beta-alanine, glutathione, and butanoate, which are involved in the inflammatory response, oxidative stress, and amino acid metabolism.ConclusionThe study suggested that LPS-induced acute liver and kidney injury mainly involves inflammatory response, oxidative stress, and protein synthesis, finally causing multi-organ damage. Correcting the disturbances to the metabolites and metabolic pathways may help to prevent and/or treat LPS-induced acute liver and kidney damage.

Dataset Information

Glomerulonephritis-induced changes in kidney gene expression in rats.

Publications

Glomerulonephritis-induced changes in kidney gene expression in rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets