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Digital spatial profiling revealed the mechanism involved in the progression of affected glomeruli in ANCA associated glomerulonephritis

ABSTRACT: Digital spatial profiling revealed the mechanism involved in the progression of affected glomeruli in ANCA associated glomerulonephritis

PROVIDER: PRJNA794108 | ENA |

REPOSITORIES: ENA

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Digital spatial profiling revealed the mechanism involved in the progression of affected glomeruli in ANCA associated glomerulonephritis [GEOmx]

Project description:We previously showed that the rupture of Bowman’s capsule (BC) promotes the progression of crescent glomerulonephritis by enhancing CD8+ T cell entry into the glomeruli. In the present study, we utilized digital spatial profiling to simultaneously profile the altered mRNA transcript and protein abundances in the glomerular and periglomerular areas of biopsy samples of ANCA-associated glomerulonephritis. The paraffin-embedded biopsy samples were stained with Collagen IV, CD45, and Syto13 to distinguish the glomeruli with crescent formation but intact BC, with focal BC rupture, and with extensive rupture of BC and glomeruli without crescent formation and leukocytes infiltration in ANCA-GN. By assessing multiple discrete glomerular areas, we found that the transcript expression level of secreted phosphoprotein 1and its receptor CD44 were upregulated significantly in the glomeruli with more severe ruptures of BC, and their expression levels correlated positively with the fibrotic markers. We also found that 1) both alternative and classic complement pathways were activated in the glomeruli from patients with ANCA-GN; 2) M1 macrophages involved mostly in the early stage of BC rupture while M2 macrophages were involved in the late stage and may contribute to the fibrosis process of the crescents, and 3) apoptosis is likely the mechanism mediating the loss of glomerular cells in ANCA-GN. Our results demonstrate that digital spatial profiling allows the comparative analysis of mRNA and protein profiles in the individual glomeruli affected differently by the disease processes and to identify potential novel mechanisms in patients with ANCA-GN.

2022-02-01 | GSE192995 | GEO

Digital spatial profiling revealed the mechanism involved in the progression of affected glomeruli in ANCA associated glomerulonephritis [RNA-Seq]

2022-02-01 | GSE192994 | GEO

Digital spatial profiling revealed the mechanism involved in the progression of affected glomeruli in ANCA associated glomerulonephritis [GEOmx]

Project description:Digital spatial profiling revealed the mechanism involved in the progression of affected glomeruli in ANCA associated glomerulonephritis [GEOmx]

| PRJNA794110 | ENA

Digital spatial profiling revealed the mechanism involved in the progression of affected glomeruli in ANCA associated glomerulonephritis [RNA-Seq]

Project description:Digital spatial profiling revealed the mechanism involved in the progression of affected glomeruli in ANCA associated glomerulonephritis [RNA-Seq]

| PRJNA794111 | ENA

CC chemokine ligand 18 (CCL18) is associated with disease activity and relapse in ANCA-associated crescentic glomerulonephritis

Project description:Anti neutrophil cytoplasmic antibody (ANCA) associated vasculitis is the most frequent cause of crescentic glomerulonephritis. Histopathologic features and clinical course of the disease are diverse and judgment of disease activity is often limited due to the lack of reliable activity markers. In order to define potentially new molecular or cellular markers in the kidney which may predict clinical outcome, we performed microarray analyses of renal biopsies from patients with ANCA-associated crescentic glomerulonephritis. We correlated expression profiles with clinical data from our prospective study of patients with renal ANCA disease. The CC chemokine ligand 18 (CCL18) was one of the most up-regulated proteins in kidneys of patients with ANCA-associated crescentic glomerulonephritis. CCL18 producing cells in the kidneys were identified as CD68 and CD209 positive myeloid dendritic cells. The density of CCL18 positive cells correlated with the severity of acute tubular injury and with the impairment of renal function. CCL18 protein levels were elevated in serum samples of patients with renal ANCA disease when compared with patients with non- ANCA-associated crescentic glomerulonephritis. Persistence of high CCL18 serum levels correlated with impairment of renal function and the risk of relapsing disease. Therefore, CCL18 might serve as a marker for persistent disease activity and renal relapses in ANCA-associated vasculitis.

2015-09-03 | E-MTAB-1944 | biostudies-arrayexpress

Digital spatial profiling revealed the mechanism involved in the progression of affected glomeruli in ANCA associated glomerulonephritis

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

2022-01-31 | GSE192996 | GEO

Single-cell TCR-sequencing of T cells in crescentic glomerulonephritis

Project description:Single-cell TCR sequencing of T cells from ANCA-associated glomerulonephritis patients and experimental crescentic glomerulonephritis mouse model.

2023-03-31 | GSE223107 | GEO

MicroRNA expression in the glomerulus of C57BL/6 mice and B6.MRLc1 glomerulonephritis mice

Project description:In isolated glomeruli by beads-perfusion methods, microRNA (miRNA) expression was analyzed in healthy C57BL/6 and B6.MRLc1 glomerulonephritis mice. The expression of 1,135 miRNAs was examined, and up-regulated or down-regulated miRNA was determined. These results provide a basical information of molecular pathology in glomerulonephritis. The glomeruli were collected from female C57BL/6 (n=3, 9-month-old, healthy control) and female B6.MRLc1 (n=3, 14-month-old, early stage of glomerulonephritis; n=3, 9-month-old, late stage of glomerulonephritis). The total RNA sample was purified, and total 1,135 microRNA expression was compared among healthy, early stage, and late stage.

2014-10-01 | E-GEOD-51209 | biostudies-arrayexpress

Glomerulonephritis in BXSB/MpJ-Yaa mice

Project description:Analysis of glomeruli isolated from kidneys of 4 month male BXSB/MpJ-Yaa. The BXSB/MpJ-Yaa mouse strain is a lupus-prone model. Results provide insight into the pathogenic mechanisms linked to glomerulonephritis in BXSB/MpJ-Yaa mice. The glomeruli were isolated from 6 BXSB/MpJ-Yaa (glomerulonephritis model) and BXSB/MpJ-Yaa+ (control). 6 glomerular populations of each strain were devided into 3 groups (1 group / 2 populations). 3 glomerulonephritis models versus 3 controls analysis was performed. BXSB/MpJ-Yaa is a recombinant inbred strain developed originally from a C57BL/6 female mouse and a SB/Le male mouse. Yaa (Y-linked autoimmune accelerator locus) localizing on the Y chromosome of BXSB/MpJ-Yaa male mice is the result of a duplication of an about 4 Mbp telomeric segment near the pseudoautosomal region of the X chromosome onto the Y chromosome. BXSB/MpJ-Yaa+ (control) male mice carry the wild-type Y chromosome in place of the mutant Yaa-containing Y chromosome of BXSB/MpJ-Yaa male mice.

2014-01-01 | E-GEOD-51230 | biostudies-arrayexpress

Glomerulonephritis in BXSB/MpJ-Yaa mice

2014-01-01 | GSE51230 | GEO

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