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Renal circadian rhythm dysregulation in lupus nephritis [RNA-seq]

ABSTRACT: Renal circadian rhythm dysregulation in lupus nephritis [RNA-seq]

PROVIDER: PRJNA545275 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9141490_1.fastq.gz	Fastqsanger.gz
	SRR9141490_2.fastq.gz	Fastqsanger.gz
	SRR9141500_1.fastq.gz	Fastqsanger.gz
	SRR9141500_2.fastq.gz	Fastqsanger.gz
	SRR9141510_1.fastq.gz	Fastqsanger.gz

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Renal circadian rhythm dysregulation in lupus nephritis

Project description:Renal circadian rhythm dysregulation in lupus nephritis

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Renal circadian rhythm dysregulation in lupus nephritis [array]

Project description:This study examines the circadian gene expression of whole kidneys of young and nephritic NZB/W F1 mice

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NCAM1: A Novel Autoantigen in Membranous Lupus Nephritis

Project description:Membranous lupus nephritis is a frequent cause of nephrotic syndrome in patients with systemic lupus erythematosus. Unlike phospholipase A2 receptor or thrombospondin type 1 domain containing 7A-associated membranous nephropathy, where known antibodies can be detected within sera by indirect immunofluorescence and/or enzyme-linked immunosorbent assay, it is not possible to monitor disease activity in membranous lupus nephritis where the target autoantigens are mostly unknown. Determination of the target autoantigen has diagnostic significance, informs prognosis, and allows for non-invasive monitoring of disease activity in serum. We utilized mass spectrometry for antigen discovery of laser capture microdissected glomeruli from formalin-fixed paraffin embedded tissue and tissue IgG immunoprecipitation studies from frozen kidney biopsy tissue. We identified neural cell adhesion molecule 1 (NCAM1) to be a target antigen in membranous lupus nephritis and within rare cases of primary membranous nephropathy. The prevalence of NCAM1-associated membranous neuropathy was 5.7% of cases of membranous lupus nephritis. NCAM1 co-localizes with IgG within glomerular immune deposits. Additionally, serum from NCAM1 patients showed reactivity to NCAM1 recombinant protein. The presence of anti-NCAM1 antibodies in sera could allow for non-invasive monitoring of the disease. We propose that NCAM1 is a target autoantigen in a subset of patients with membranous lupus nephritis. Future studies are needed to determine whether anti-NCAM1 antibody levels correlate with disease activity or response to therapy.

2020-10-19 | PXD021123 | Pride

Reversible dysregulation of renal circadian rhythm in lupus nephritis.

Project description:BackgroundWe have found disruption of expression of major transcriptional regulators of circadian rhythm in the kidneys of several mouse models of lupus nephritis. Here we define the consequence of this disturbance with respect to circadian gene expression and renal homeostatic function in a mouse model of lupus nephritis.MethodsMolecular profiling of kidneys from 47 young and 41 nephritic female NZB/W F1 mice was performed at 4 hourly intervals over a 24 h period. Disruption of major circadian transcriptional regulators was confirmed by qPCR. Molecular data was normalized and analyzed for rhythmicity using RAIN analysis. Serum aldosterone and glucose and urine sodium and potassium were measured at 4 hourly intervals in pre-nephritic and nephritic mice and blood pressure was measured every 4 h. Analyses were repeated after induction of complete remission of nephritis using combination cyclophosphamide and costimulatory blockade.ResultsWe show a profound alteration of renal circadian rhythms in mice with lupus nephritis affecting multiple renal pathways. Using Cosinor analysis we identified consequent alterations of renal homeostasis and metabolism as well as blood pressure dipper status. This circadian dysregulation was partially reversed by remission induction therapy.ConclusionsOur studies indicate the role of inflammation in causing the circadian disruption and suggest that screening for loss of normal blood pressure dipping should be incorporated into LN management. The data also suggest a potential role for circadian agonists in the treatment of lupus nephritis.

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Renal circadian rhythm dysregulation in lupus nephritis

Project description:This SuperSeries is composed of the SubSeries listed below.

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Effect of Sirolimus treatment on lupus nephritis in NZB/W F1 female mice

Project description:NZB/WF1 female mice spontaneously develop autoimmune lupus nephritis. Expression profiling of kidney tissue from (a) 12 week NZB/W F1 female mice defined as asymptomatic for lupus nephritis, (b) 36 and 42 week NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 and 42 week NZB/W F1 female mice that are diseased/symptomatic for lupus nephritis and treated with Sirolimus was carried out. The goal of the study was to identify genes associated with lupus nephritis and modulated by Sirolimus, an inhibitor of mTOR. In addition, lupus nephritis genes resistant to Sirolimus therapy were also identfied This series of samples comprises of kidney tissue from (a) 12 week old NZB/W F1 female mice defined as asymptomatic for lupus nephritis (N=4), (b) 36 (N=3) and 42 week (N=3) old NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 (N=3)and 42 (N=3) week old NZB/W F1 female mice that are asymptomatic for lupus nephritis on treatment with Sirolimus

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Identification of unique microRNA signature associated with lupus nephritis

Project description:MicroRNAs (miRNA) have emerged as an important new class of modulators of gene expression. In this sudy we investigated miRNA that are differentially expressed in lupus nephritis. Microarray technology was used to investigate differentially expressed miRNA in PBMCs and EBV-transformed cell lines obtained from lupus nephritis patients and controls. TaqMan-based stem-loop real-time PCR was used for validation. Microarray analysis of miRNA expressed in African Americans (AA) derived lupus nephritis samples revealed 29 differentially expressed miRNA, of 850 tested. Microarray analysis of miRNA expressed in European American (EA) derived lupus nephritis samples revealed 50 differentially expressed miRNA, of 850 tested.

2011-12-30 | GSE21384 | GEO

Effect of Sirolimus treatment on lupus nephritis in NZB/W F1 female mice

2008-11-21 | GSE12024 | GEO