Effects of a Tricaprylin Emulsion on Anti-glomerular Basement Membrane Glomerulonephritis in Rats
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Akira Hirasawa
PROVIDER: E-GEOD-46295 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Expression data from rat with anti-glomerular basement membrane nephritis (anti-GBM). We used microarrays to analyze the transcriptome of kidney from anti-GBM model rat with or without drug treatment
2015-07-14 | GSE46295 | GEO
Project description:We analyzed the impact of the genetic background during experimental passive non-accelerated anti-glomerular basement membrane glomerulonephritis (anti-GBM-GN) (an equivalent to nephrotoxic nephritis) in two different mouse genetic backgrounds (C57BL6/J vs 129S2svPAS/crl). Glomerular extracts have been made at an early time point (e.g day 4 of the induction of the glomerulonephritis). RNA have been extracted following standard procedures.
2014-07-14 | GSE56236 | GEO
Project description: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. 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. 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. 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. Two different rat strains (WKY and SD) were dosed with different doses of NTS and after 14 days rats were euthanized and kidneys were removed for RNA extraction and hybridization on Affymetrix microarrays. We sought to analyze the deregulation of gene expression during NTS-induced glomerulonephritis and to compare the effect in the two rat strains.
2015-07-06 | E-GEOD-64265 | biostudies-arrayexpress
Project description:The glomerular filtration barrier prevents large serum proteins from being lost into the urine. It is not known, however, why the filter does not routinely clog with large proteins that enter the glomerular basement membrane (GBM). Here we provide evidence that an active transport mechanism exists to remove immunoglobulins that accumulate at the filtration barrier. We found that FcRn, an IgG and albumin transport receptor, is expressed in podocytes and functions to internalize IgG from the GBM. Mice lacking FcRn accumulated IgG in the GBM as they aged and tracer studies showed delayed clearance of IgG from the kidneys of FcRn deficient mice. Supporting a role for this pathway in disease, saturating the clearance mechanism potentiated the pathogenicity of nephrotoxic sera. These studies support the idea that podocytes play an active role in removing proteins from the GBM and suggest that genetic or acquired impairment of the clearance machinery is likely to be a common mechanism promoting glomerular diseases. Keywords: Unique cell type expression analysis
2008-01-01 | GSE10017 | GEO
Project description: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. 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. 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 β-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. 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.
2015-07-06 | GSE64265 | GEO
Project description:A 46-year-old female presented with a chief complaint of fatigue and intermittent painless gross hematuria for one month. The patient was fluid overloaded on physical examination and noted to be in acute renal failure with a serum creatinine of 10.8 mg/dL. The patient was emergently started on hemodialysis. Serologies were negative for antinuclear antibody (ANA), anti-neutrophilic cytoplasmic antibody (ANCA), and anti-glomerular basement membrane (anti-GBM) antibody. However, renal biopsy revealed 90% glomerular involvement by temporally heterogeneous crescents ranging from cellular to fibrous. Immunofluorescence studies revealed strong, linear glomerular capillary wall staining for immunoglobulin G (IgG). Although the patient was treated with pulse dose steroids and cyclophosphamide, the patient ultimately developed infectious complications from immunosuppression, and treatment was terminated. This case highlights the atypical presentation of anti-GBM disease diagnosed based on renal biopsy with negative serologies. Although rare, the possibility of atypical anti-GBM antibodies which are not detected by standard commercial assays should be considered in such cases.
| S-EPMC6603348 | biostudies-literature
Project description:The glomerular filtration barrier prevents large serum proteins from being lost into the urine. It is not known, however, why the filter does not routinely clog with large proteins that enter the glomerular basement membrane (GBM). Here we provide evidence that an active transport mechanism exists to remove immunoglobulins that accumulate at the filtration barrier. We found that FcRn, an IgG and albumin transport receptor, is expressed in podocytes and functions to internalize IgG from the GBM. Mice lacking FcRn accumulated IgG in the GBM as they aged and tracer studies showed delayed clearance of IgG from the kidneys of FcRn deficient mice. Supporting a role for this pathway in disease, saturating the clearance mechanism potentiated the pathogenicity of nephrotoxic sera. These studies support the idea that podocytes play an active role in removing proteins from the GBM and suggest that genetic or acquired impairment of the clearance machinery is likely to be a common mechanism promoting glomerular diseases. Experiment Overall Design: Total RNA for genechip analysis was derived from two sources: Experiment Overall Design: 1) Primary mouse podocytes isolated by FACS sorting of collagenase digested glomeruli Experiment Overall Design: 2) In vitro differentiated conditionally immortalized mouse podocyte cell line. Experiment Overall Design: After obtaining genechip data, the expression of various IgG and albumin receptors was queried in the genechip data and then confirmed by RT-PCR.
2008-06-11 | E-GEOD-10017 | biostudies-arrayexpress
Project description:IntroductionAnti-glomerular basement membrane (anti-GBM) disease is a severe entity with few therapeutic options including plasma exchange and immunosuppressive agents. The aim of this study was to analyze the clinical and pathological features that predict the evolution of end-stage kidney disease (ESKD) and the kidney survival in a cohort of patients with anti-GBM disease with renal involvement in real life.MethodsA retrospective multicentre observational study including 72 patients from 18 nephrology departments with biopsy-proven anti-GBM disease from 1999 to 2019 was performed. Progression to ESKD in relation to clinical and histological variables was evaluated.ResultsCreatinine at admission was 8.6 (± 4) mg/dL and 61 patients (84.7%) required dialysis. Sixty-five patients (90.3%) underwent plasma exchange. Twenty-two patients (30.6%) presented pulmonary hemorrhage. Kidney survival was worse in patients with creatinine levels > 4.7 mg/dL (3 vs. 44% p < 0.01) and in patients with > 50% crescents (6 vs. 49%; p = 0.03). Dialysis dependence at admission and creatinine levels > 4.7 mg/dL remained independent significant predictors of ESKD in the multivariable analysis [HR (hazard ratio) 3.13 (1.25-7.84); HR 3 (1.01-9.14); p < 0.01]. The discrimination value for a creatinine level > 4.7 mg/dL and 50.5% crescents had an area under the curve (AUC) of 0.9 (95% CI 0.82-0.97; p < 0.001) and 0.77 (95% CI 0.56-0.98; p = 0.008), respectively. Kidney survival at 1 and 2 years was 13.5 and 11%, respectively. Patient survival at 5 years was 81%.ConclusionIn real life, patients with severe anti-GBM disease (creatinine > 4.7 mg/dL and > 50% crescents) remained with devastating renal prognosis despite plasma exchange and immunosuppressive treatment. New therapies for the treatment of this rare renal disease are urgently needed.
| S-EPMC9295717 | biostudies-literature
Project description:Different mosue strains showed different sensitivity to anti-GBM antibody induced glomerulai nephritis. By analyze the renal gene expressin profiles in different mouse stains after challenging with anti-GBM antibody, we will be able to identify the genes and pathway underlining the anti-GBM nephritis.
2013-12-24 | GSE53611 | GEO
Project description:We demonstrated that in anti-glomerular basement membrane (anti-GBM) glomerulonephritis, crescents derived from clonal amplification of an immature subset of parietal epithelial cells (PECs) and that following treatment of mice with 3 different drugs currently used in haematological stem cell disorders (panobinostat, givinostat and ruxolitinib), only panobinostat exerted beneficial effect. To establish the mechanism of action of panobinostat, we generated single-cell RNA sequencing (scRNAseq) datasets of kidney cells obtained from control mice with anti-GBM glomerulonephritis and of mice treated with the three drugs. The analysis demonstrated that the drugs exerted similar effects on clusters of cells of the immune system, suggesting that all the three drugs elicit similar anti-inflammatory and immunosuppressive properties.
2022-09-24 | GSE195784 | GEO