Expression data from kidney biopsies of patients with chronic liver disease
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE205645 | GEO | 2022/06/12
REPOSITORIES: GEO
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Project description:The biopsy samples obtained at implantation segregated in 2 distinct groups according to donor origin, with a cluster of 319 unique identified genes higher expressed in DD compared to LD kidneys, and 329 genes lower expressed (false discovery rate <5%). Using pathway analysis software a significant local renal overrepresentation of complement genes in DD implantation biopsies was identified. Complement gene expression in DD kidneys related both to donor death and cold ischemia duration, and was associated with a slower onset of renal allograft function. In post-transplantation protocol biopsies, there was a continued overexpression of complement genes, regardless of donor source. The local renal complement gene expression variability in post-transplantation biopsies correlated with renal graft function. This study demonstrates a significant and clinically relevant local overexpression of complement genes in DD kidneys at engraftment and continuous functionally important regulation of complement gene expression after transplantation, regardless of donor source. Targeted therapy interfering with complement activation is an attractive therapeutic target that deserves further investigation in solid organ transplantation. Keywords: time course, genomics gene expression
2008-04-16 | GSE11166 | GEO
Project description:The biopsy samples obtained at implantation segregated in 2 distinct groups according to donor origin, with a cluster of 319 unique identified genes higher expressed in DD compared to LD kidneys, and 329 genes lower expressed (false discovery rate <5%). Using pathway analysis software a significant local renal overrepresentation of complement genes in DD implantation biopsies was identified. Complement gene expression in DD kidneys related both to donor death and cold ischemia duration, and was associated with a slower onset of renal allograft function. In post-transplantation protocol biopsies, there was a continued overexpression of complement genes, regardless of donor source. The local renal complement gene expression variability in post-transplantation biopsies correlated with renal graft function. This study demonstrates a significant and clinically relevant local overexpression of complement genes in DD kidneys at engraftment and continuous functionally important regulation of complement gene expression after transplantation, regardless of donor source. Targeted therapy interfering with complement activation is an attractive therapeutic target that deserves further investigation in solid organ transplantation. Keywords: time course, genomics gene expression A total of 95 human renal allograft protocol biopsies were included in this study, 28 biopsies (14 DD, 14 LD) obtained at implantation prior to revascularization and 67 protocol biopsies obtained after transplantation. Whole genome expression profiles were assessed using microarrays. This dataset is part of the TransQST collection.
2008-04-16 | E-GEOD-11166 | biostudies-arrayexpress
Project description:Glomerular abnormalities have been demonstrated in kidney biopsies of patient after orthotopic liver transplantation (OLT). We hypothesize that these changes exist prior to OLT and may play a role in the development of renal failure after OLT. We use gene expression microarrays to investigate the mechanism of kidney disease in patients listed for OLT. Gene expression profiles of biopsies of cirrhotic patients were compared with pre-implantation living donor biopsies. Glomerular abnormalities were seen in 92% of the biopsies, the most common being increase in mesangial matrix. Electron microscope showed effacement of podocytes (93%) and duplication (35%) and widening of glomerular basement membrane (45%). Gene Ontology analysis revealed significant up-regulation of genes implicated in immune response, including T-cell, leucocyte and platelet activation and differentiation. Pathogenesis-based transcripts analysis revealed significantly increased expression of cytotoxic T-cell, macrophage, B-cell, natural killer cell, and endothelial cell associated transcripts, indicating an ongoing inflammatory immune response. Eight patients with cirrhotic livers listed for transplantation were referred to the kidney transplant clinic at Montefiore Medical Center, Bronx, New York, for evaluation of renal dysfunction between April 2010 and March 2013. Patients consented prior to clinically indicated kidney biopsy for enrollment into the study. Information and lab results were collated for each patient including: age, sex, race, etiology of liver disease, history of diabetes mellitus (DM) and hypertension (HTN), metabolic profile, liver function tests, glycosylated hemoglobin (HgbA1c), C3 and C4 complement concentrations, antinuclear antibody titers and spot urine protein to creatinine ratio. Patients completed a 24-hr urine collection for protein and creatinine, which was used to assess proteinuria and creatinine clearance. eGFR was calculated using the Modified Diet of Renal Disease (MDRD) formula. Hematuria was defined as presence of any red cells in urine analysis. Proteinuria was defined as protein excretion of greater than 100mg in 24 hour. HTN and DM were defined by use of anti-hypertensive and insulin or oral hypoglycemic agents respectively in past or at time of kidney biopsy. Biopsies from cirrhotic patients were then compared to nine pre-implantation biopsies from living kidney donors. The de-identified patient clinical characteristics are provided in each sample records; For Hematuria, HTN, MM (mesangial matrix expansion), MC (mesangial cell increase), II (interstitial inflammation), podocyte, BM (basement membrane thickening), the value 0 and 1 represents 'ABSENT' and 'PRESENT', respectively. For C3 and C4, the value 0 and 1 represents NORMAL and LOW C3 (or C4) LEVELS, repectively. For TA (tubular atrophy), IF (interstital fibrosis), AS (arteiosclerosis), the value 0, 1, and 2 represents ABSENT, PRESENT MILD, and PRESENT MODERATE, respectively. For IgG, IgA, IgM, C, and EmPE, the values represent 1 (ABSENT), 1 (MILD STAINING), 2 (MODERATE), 3 (SEVERE), NA (NOT AVAILABLE), P (PENDING). For BMWId, BMd, and EDD, the values represent 0 (ABSENT), 1 (PRESENT), NA (NOT AVAILABLE), P (PENDING).
2013-09-17 | E-GEOD-50892 | biostudies-arrayexpress
Project description:We aimed to identify miRNA biomarkers of renal injury in kidney biopsies from patients with lupus nephritis. MiRNA profiles of 8 patients were analyzed for correlation with various clinical features including Progression, Activity, Chronicity, and Time to Kidney Failure. MicroRNAs (miRs) are promising biomarkers and are involved in pathogenesis of kidney diseases. We aimed to identify miR biomarkers of renal injury in kidney biopsies from patients with lupus nephritis and study their potential role in renal fibrosis. miR-150 was significantly increased in kidneys with high chronicity compared to low chronicity and it correlated positively with chronicity index scores and renal collagen I expression. In kidneys with high chronicity, miR-150 was found predominantly in proximal tubular cells (PTCs) and was moderately expressed in podocytes and to lesser degree in mesangial cells (MCs). We hypothesized that miR-150 increases fibrosis by downregulating a negative regulator of profibrotic proteins. Suppressor of cytokine signaling1 (SOCS1) is a predicted target of miR-150 and has shown antifibrotic role. After confirming that SOCS1 is a direct target of miR-150, we showed that transfection of a miR-150 analog downregulated SOCS1 protein and upregulated the profibrotic proteins fibronectin, collagen I, collagen III, and TGF-β1 in both primary normal human renal PTCs and MCs. A similar effect was seen when using a SOCS1 siRNA to confirm that the effect of miR-150 on profibrotic proteins is mediated through SOCS1. Stimulation with TGF-β1 induced miR-150 increase in PTCs and human podocytes but not MCs. These results suggest that miR-150 might be a useful quantitative renal biomarker of kidney injury in lupus nephritis and that miR-150, which might be partially induced by TGF-β1, plays an important role in renal fibrosis by increasing profibrotic molecules through downregulation of SOCS1. FFPE kidney specimens (n=25) including baseline and repeated needle renal biopsies were from 14 patients with LN enrolled in IRB-approved protocols at the NIDDK between 1976 and 1999. The specimens were divided in two groups based on histological chronicity index (CI). CI ≥ 4 were categorized as having high degree of chronicity of chronic kidney injury. 18 kidneys from 8 patients including high CI (n=9) and low CI (n=9) were used for miR profiling by Affymetrix microRNA microarrays.
2012-12-01 | E-GEOD-42648 | biostudies-arrayexpress
Project description:We aimed to identify miRNA biomarkers of renal injury in kidney biopsies from patients with lupus nephritis. MiRNA profiles of 8 patients were analyzed for correlation with various clinical features including Progression, Activity, Chronicity, and Time to Kidney Failure. MicroRNAs (miRs) are promising biomarkers and are involved in pathogenesis of kidney diseases. We aimed to identify miR biomarkers of renal injury in kidney biopsies from patients with lupus nephritis and study their potential role in renal fibrosis. miR-150 was significantly increased in kidneys with high chronicity compared to low chronicity and it correlated positively with chronicity index scores and renal collagen I expression. In kidneys with high chronicity, miR-150 was found predominantly in proximal tubular cells (PTCs) and was moderately expressed in podocytes and to lesser degree in mesangial cells (MCs). We hypothesized that miR-150 increases fibrosis by downregulating a negative regulator of profibrotic proteins. Suppressor of cytokine signaling1 (SOCS1) is a predicted target of miR-150 and has shown antifibrotic role. After confirming that SOCS1 is a direct target of miR-150, we showed that transfection of a miR-150 analog downregulated SOCS1 protein and upregulated the profibrotic proteins fibronectin, collagen I, collagen III, and TGF-β1 in both primary normal human renal PTCs and MCs. A similar effect was seen when using a SOCS1 siRNA to confirm that the effect of miR-150 on profibrotic proteins is mediated through SOCS1. Stimulation with TGF-β1 induced miR-150 increase in PTCs and human podocytes but not MCs. These results suggest that miR-150 might be a useful quantitative renal biomarker of kidney injury in lupus nephritis and that miR-150, which might be partially induced by TGF-β1, plays an important role in renal fibrosis by increasing profibrotic molecules through downregulation of SOCS1.
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2011-07-12 | GSE30576 | GEO
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