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.
Project description:In this study, we employed high-throughput RNA sequencing (RNA-Seq) to identify the Smad3-dependent lncRNAs related to renal inflammation and fibrosis in Smad3 knockout (KO) mouse models of unilateral ureteral obstructive nephropathy (UUO) and immunologically-induced anti-glomerular basement membrane glomerulonephritis (anti-GBM GN).
Project description:In this study, we employed high-throughput RNA sequencing (RNA-Seq) to identify the Smad3-dependent lncRNAs related to renal inflammation and fibrosis in Smad3 knockout (KO) mouse models of unilateral ureteral obstructive nephropathy (UUO) and immunologically-induced anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). 12 kidney tissue samples of Smad3 KO/WT mice from normal control, UUO at day 5 or anti-GBM GN at day 10 models (n=2 in each group) for whole transcriptome RNA-sequencing.
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.
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
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 RNA from whole kidneys was extracted and processed for hybridization on Affymetrix microarrays.
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.
Project description:The glucocorticoid-inducible protein annexin A1 has been shown to function as key-regulator of the resolution phase of inflammation but its role in immune-mediated crescentic glomerulonephritis has not been studied so far. Acute crescentic glomerulonephritis was induced in annexin A1 deficient and wildtype mice using a sheep serum against rat glomerular basement membrane constituents. Alterations in gene expression were determined by RNA-Seq and gene ontology analysis. Intrinsic annexin A1 has a protective effect in reducing pro-inflammatory signals and infiltration of neutrophil granulocytes during crescentic GN. The annexin A1 signaling cascade may therefore provide novel targets for the treatment of inflammatory kidney disease.
Project description:The Wistar-Kyoto (WKY) rat shows marked susceptibility to crescentic glomerulonephritis, while Lewis rats are resistant. Glomerular injury and crescent formation are macrophage-dependent. The aim of this study is to use gene expression profiling to identify genetic factors that determine macrophage activation and render WKY rats susceptibile to glomerulonephritis.
