Altered modulation of WNT-β-catenin and PI3K/Akt pathways in IgA nephropathy
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE14795 | GEO | 2010/05/26
SECONDARY ACCESSION(S): PRJNA112079
REPOSITORIES: GEO
Similar Datasets
Project description:To uncover new molecular mechanisms involved in IgAN pathogenesis, we compared the genomic profiles of 12 IgAN patients with 8 healthy subjects, We included addiotional disease controls 3 FSGS(Focal Segmenal glomerulosclerosis) patients and 3 membrano proliferative glomerulonephritis type I (MPGN-I) controls in our study to evaluate if the WNT-β-catenin and PI3K/Akt pathways were specfic to IgAN. Gene expression profile comparison between 12IgAN patients and 8 Healthy Subjects. Gene Set Enrichment Analysis (GSEA) performed on the additional disease controls determined that the a priori defined set of genes and the pathways generated were specific to the IgAN
2010-06-08 | E-GEOD-14795 | biostudies-arrayexpress
Project description:Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 albumin-regulated genes differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n=25) could be distinguished from those of control subjects (n=6) based solely upon the expression of these 231 albumin-regulated genes. The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that the all forms of primary glomerulonephritis (n=33) can be distinguished from controls (n=21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis. We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with IgA nephropathy (IgAN) RNA from tubulointerstitial compartments was extracted and processed for hybridization on Affymetrix HG-U133A microarrays.
2012-02-02 | E-GEOD-35487 | biostudies-arrayexpress
Project description:Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 albumin-regulated genes differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n=25) could be distinguished from those of control subjects (n=6) based solely upon the expression of these 231 albumin-regulated genes. The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that the all forms of primary glomerulonephritis (n=33) can be distinguished from controls (n=21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis. We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with IgA nephropathy (IgAN) RNA from tubulointerstitial compartments was extracted and processed for hybridization on Affymetrix HG-U133A microarrays.
2012-02-02 | E-GEOD-35488 | biostudies-arrayexpress
Project description:Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 albumin-regulated genes differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n=25) could be distinguished from those of control subjects (n=6) based solely upon the expression of these 231 albumin-regulated genes. The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that the all forms of primary glomerulonephritis (n=33) can be distinguished from controls (n=21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis. We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with IgA nephropathy (IgAN)
2012-02-02 | GSE35488 | GEO
Project description:Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 albumin-regulated genes differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n=25) could be distinguished from those of control subjects (n=6) based solely upon the expression of these 231 albumin-regulated genes. The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that the all forms of primary glomerulonephritis (n=33) can be distinguished from controls (n=21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis. We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with IgA nephropathy (IgAN)
2012-02-02 | GSE35487 | GEO
Project description:Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis involves both genetic and environmental factors. DNA methylation, the most studied epigenetic modification, was shown to play a role in IgAN. In two pairs of IgAN-discordant monozygotic (MZ) twins, here we assessed genome-wide DNA methylation profiling and gene expression profiling in order to characterize DNA methylation changes in IgAN and their potential influences on gene expression.
2021-05-15 | GSE151454 | GEO
Project description:Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis involves both genetic and environmental factors. DNA methylation, the most studied epigenetic modification, was shown to play a role in IgAN. In two pairs of IgAN-discordant monozygotic (MZ) twins, here we assessed genome-wide DNA methylation profiling and gene expression profiling in order to characterize DNA methylation changes in IgAN and their potential influences on gene expression.
2021-05-15 | GSE151456 | GEO
Project description:Purpose: Immunoglobulin A nephropathy (IgAN) is immune-mediated primary glomerulonephritis, which is the most common reason leading to renal failure worldwide, the exact pathogenesis of IgAN is not well defined. Accumulating evidence indicates that circular RNAs (circRNAs) play crucial roles in the immune disease by involving in the competing endogenous RNA (ceRNA) network mechanism. At present, the studies of the circRNA profiles and circRNA-associated ceRNA networks in the IgAN are still scarce. This study aimed to elucidate the potential roles of circRNA, microRNA (miRNA), and messenger RNA (mRNA) ceRNA network in peripheral blood mononuclear cells (PBMCs) of IgAN. Methods: CircRNA sequencing was used to identify the differential expressed circRNAs (DEcircRNAs) of PBMCs in IgAN and healthy controls. A circRNA-miRNA-mRNA ceRNA network was constructed to further investigate the mechanisms of IgAN. Results: A total of 145 circRNAs were differentially expressed in IgAN compared with controls (|log2 (FC)|>1 and P-value <0.05). Combined with the data from GSE73953 and GSE25590 in GEO database, a ceRNA network was constructed which contained 16 DEcircRNAs, 72 differential expressed mRNAs (DEmRNAs) and 11 differential expressed miRNAs (DEmiRNAs). Conclusion: Our study identified a novel circRNA-mediated ceRNA regulatory network mechanisms in the pathogenesis of IgAN.
2020-11-08 | GSE154046 | GEO
Project description:Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. However, biomarkers for predicting the progression or regression of IgAN remain a clinical challenge. In the present study, we aim to identify novel diagnostic and prognostic markers of IgAN. Using the cytokine antibody array, we detected serum and urinary levels of nine potential IgAN biomarkers in 32 IgAN patients and 16 healthy controls. The IgAN patients were grouped according to Lee’s grading system, with 16 patients with Grade I–II in the mild IgAN group and 16 with Grade III-V in the severe IgAN group. The associations between levels of these markers and IgAN were evaluated.
2022-07-13 | E-MTAB-11972 | biostudies-arrayexpress
Project description:Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide characterized by aberrant O-glycosylation in the hinge region of IgA1. The basis for the abnormal glycosylation in IgAN is still unknown, but an important involvement of the enzyme core 1, beta 1,3-galactosyltransferase 1 (C1GALT1) is known. However, the role of microRNAs (miRNAs), a new family of key mRNA regulatory molecules, in the IgAN pathogenesis has not yet been reported. In this study, by high-throughput microRNA profiling, we identified 37 miRNAs differentially expressed in peripheral blood mononuclear cells (PBMCs) from IgAN patients compared to healthy subjects. Among them, upregulated miR-148b potentially targeted C1GALT1, INVS and PTEN, three genes notably downregulated in IgAN patients. C1GALT1 expression levels in IgAN patients were reduced and negatively correlated with the upregulated miR-148b expression. We demonstrated the biological relationship between miR-148b and C1GALT1 by transient transfection experiments ex vivo. When we reduced the upregulated miR-148b function in PBMCs of IgAN patients an increase of the C1GALT1 mRNA and protein levels was observed. We validated biologically also the miR-148b targeting of INVS , involved in the altered modulation of the WNT–β-catenin and PI3K/Akt pathways in IgAN patients. All together our data evidence an important role of miR-148b in the pathogenesis of IgAN, which could explain the aberrant glycosylation of IgA1 in the pathogenesis and should light on a potential target for the theraphy of the disease.
2012-03-12 | GSE25590 | GEO