Expression data from kidney biopsies of liver disease patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE50892 | GEO | 2013/09/17
SECONDARY ACCESSION(S): PRJNA219308
REPOSITORIES: GEO
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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:Molecular characterization of the individual cell types in human kidney as well as model organisms are critical in defining organ function and understanding translational aspects of biomedical research. Previous studies have uncovered gene expression profiles of several kidney glomerular cell types, however, important cells, including mesangial (MCs) and glomerular parietal epithelial cells (PECs), were missing or incompletely described, and a systematic comparison between mouse and human kidney is lacking. To this end, we used Smart-seq2 to profile 4332 individual glomerulus-associated cells isolated from human living donor renal biopsies and mouse kidney. The analysis revealed genetic programs for all four glomerular cell types (podocytes, glomerular endothelial cells, MCs and PECs) as well as rare glomerulus-associated macula densa cells (MDCs). Importantly, we detected heterogeneity in glomerulus-associated Pdgfrb-expressing cells, including bona fide intraglomerular MCs with the functionally active phagocytic molecular machinery, as well as a unique mural cell type located in the central stalk region of the glomerulus tuft. Furthermore, we observed remarkable species differences in the individual gene expression profiles of defined glomerular cell types that highlight translational challenges in the field and provide a guide to design translational studies.
2020-11-21 | GSE160048 | GEO
Project description:Glomerular diseases are the leading cause of chronic kidney diseases with pathomechanisms largely unclear. It is known that ANGPT2 regulates endothelial cell homeostasis and function via TEK/TIE2 and its deregulation causes endothelial damage. We found that ANGPT2 is upregulated in glomerular diseases and wondered whether it has any effect on glomerular podocytes and mesangial cells given that they have no or low TEK expression. We treated podocytes and mesangial cells in culture with ANGPT2 and found no overt cellular changes. RNA-seq analysis showed that gene expression was altered in both podocytes and mesangial cells and that the regulated genes in the two cell types were fundamentally different. GO and KEGG analyses showed that the two groups of regulated genes were enriched in distinct processes and pathways. These results suggest that ANGPT2 exerts effects on both podocytes and mesangial cells and that increased ANGPT2 may be involved in glomerular injury by affecting podocytes and mesangial cells in addition to endothelial cells.
2022-01-10 | GSE185292 | GEO
Project description:Glomerular diseases are the leading cause of chronic kidney diseases with pathomechanisms largely unclear. It is known that ANGPT2 regulates endothelial cell homeostasis and function via TEK/TIE2 and its deregulation causes endothelial damage. We found that ANGPT2 is upregulated in glomerular diseases and wondered whether it has any effect on glomerular podocytes and mesangial cells given that they have no or low TEK expression. We treated podocytes and mesangial cells in culture with ANGPT2 and found no overt cellular changes. RNA-seq analysis showed that gene expression was altered in both podocytes and mesangial cells and that the regulated genes in the two cell types were fundamentally different. GO and KEGG analyses showed that the two groups of regulated genes were enriched in distinct processes and pathways. These results suggest that ANGPT2 exerts effects on both podocytes and mesangial cells and that increased ANGPT2 may be involved in glomerular injury by affecting podocytes and mesangial cells in addition to endothelial cells.
2022-01-10 | GSE185293 | GEO
Project description:IgA nephropathy (IgAN) is the most common glomerulonephritis in the world. The disease is characterized by galactose deficient IgA (gd-IgA) in the circulation forming immune complexes. The complexes are deposited in the glomerular mesangium leading to inflammation and loss of renal function, but the pathophysiology of the disease is still not fully understood. Using an integrated global transcriptomic and proteomic profiling approach we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsies from patients with IgAN. The influence of galactose deficient IgA (gd-IgA) on mesangial cells was investigated by proteomic profiling. By utilizing the previous published literature curated glomerular cell type-specific genes, we found that mesangial cells and their positive standard genes play a more dominant role in IgAN comparing to the podocyte standard genes. Additionally, the patient clinical parameters (serum creatinine values and estimated glomerular filtration rate - eGFR) significantly correlate with z-scores derived from expression profile of mesangial cell positive standard genes. 22 common pathways were identified both from in vivo microarray data and in vitro mesangial cell mass spectrometry data and the main part was inflammatory pathways. The correlation between clinical data and mesangial standard genes allows for a better understanding of the onset of IgAN. The genes, proteins and their corresponding pathways identified in this paper give us novel insights into the pathophysiological mechanisms leading to progression of IgAN. RNA from glomerular compartment was extracted and processed for hybridization on Affymetrix microarrays. This dataset is part of the TransQST collection.
2017-07-03 | E-GEOD-93798 | biostudies-arrayexpress
Project description:Objective – Previous studies showed that genetic deletion or pharmacological blockade of the Receptor for Advanced Glycation Endproducts (RAGE) prevents the early structural changes in the glomerulus associated with diabetic nephropathy (DN). To overcome limitations of mouse models that lack the progressive glomerulosclerosis observed in humans, we studied the contribution of RAGE to DN in the OVE26 type 1 mouse, a model of progressive glomerulosclerosis and decline of renal function. Research Design and Methods – We bred OVE26 mice with homozygous RAGE knock out (RKO) mice and examined structural changes associated with DN and used inulin clearance studies and albumin:creatinine measurements to assess renal function. Affymetrix Mouse 430.2 microarrays were used to measure the differential expression of OVE26vsFVB(WT) mice. Transcriptional changes in the TGF-?1 and Plasminogen activator inhibitor 1 gene products were measured by pcr to investigate mechanisms underlying accumulation of mesangial matrix in OVE26 mice. Results - Deletion of RAGE in OVE26 mice reduced nephromegaly, mesangial sclerosis, cast formation, glomerular basement membrane thickening, podocyte effacement, and albuminuria. The significant 29% reduction in glomerular filtration rate observed in OVE26 mice was completely prevented by deletion of RAGE. Increased transcription of the genes for Plasminogen activator inhibitor 1, TGF-?1, TGF-? induced, ?1- (IV) collagen observed in OVE26 renal cortex significantly reduced in OVE26 RKO kidney cortex. ROCK1 activity was significantly lower in OVE26 RKO compared to OVE26 kidney cortex. Conclusions - These data provide compelling evidence for critical roles for RAGE in the pathogenesis of DN and suggest that strategies targeting RAGE in long-term diabetes may prevent loss of renal function. The differential gene expression of OVE26 (diabetics) vs FVB (nodiabetic WT) mice was measured using Affymetrix Mouse 430.2 arrays.
2011-02-22 | E-GEOD-20844 | biostudies-arrayexpress
Project description:Background: Recent single-cell RNA sequencing (scRNA-seq) analyses have offered much insight into cell-specific gene expression profiles in normal kidneys. However, in diseased kidneys, understanding of changes in specific cells, particularly glomerular cells, remains limited. Methods: To elucidate the glomerular cell–specific gene expression changes in diabetic kidney disease, we performed scRNA-seq analysis of isolated glomerular cells from streptozotocin-induced diabetic endothelial nitric oxide synthase (eNOS)–deficient (eNOS-/-) mice and control eNOS-/- mice. Results: We identified five distinct cell populations, including glomerular endothelial cells, mesangial cells, podocytes, immune cells, and tubular cells. Using scRNA-seq analysis, we confirmed the expression of glomerular cell–specific markers and also identified several new potential markers of glomerular cells. The number of immune cells was significantly higher in diabetic glomeruli compared with control glomeruli, and further cluster analysis showed that these immune cells were predominantly macrophages. Analysis of differential gene expression in endothelial and mesangial cells of diabetic and control mice showed dynamic changes in the pattern of expressed genes, many of which are known to be involved in diabetic kidney disease. Moreover, gene expression analysis showed variable responses of individual cells to diabetic injury. Conclusion: Our findings demonstrate the ability of scRNA-seq analysis in isolated glomerular cells from diabetic and control mice to reveal dynamic changes in gene expression in diabetic kidneys, with variable responses of individual cells. Such changes, which might not be apparent in bulk transcriptomic analysis of glomerular cells, may help identify important pathophysiologic factors contributing to the progression of diabetic kidney disease.
2019-03-08 | GSE127235 | GEO
Project description:Transforming growth factor‐beta (TGF‐β1) plays an important regulatory role in the progression of chronic kidney failure. Further, damage to kidney glomerular mesangial cells is central to the progression of diabetic nephropathy. The aim of this study was to explore the genetic associations between mRNA, microRNA, and epigenetics in mesangial cells in response to TGF‐β1. The regulatory effects of TGF‐β1 on mesangial cells were investigated at different molecular levels by treating mesangial cells with TGF‐β1 for 3 days followed by genome‐wide miRNA, RNA, MeDIP-seq, and H3K27Me3 expression profiling using next-generation sequencing (NGS). Each sample was designed with 3 repeat samples.
2018-10-24 | GSE121701 | GEO
Project description:Transforming growth factor‐beta (TGF‐β1) plays an important regulatory role in the progression of chronic kidney failure. Further, damage to kidney glomerular mesangial cells is central to the progression of diabetic nephropathy. The aim of this study was to explore the genetic associations between mRNA, microRNA, and epigenetics in mesangial cells in response to TGF‐β1. The regulatory effects of TGF‐β1 on mesangial cells were investigated at different molecular levels by treating mesangial cells with TGF‐β1 for 3 days followed by genome‐wide miRNA, RNA, MeDIP-seq, and H3K27Me3 expression profiling using next-generation sequencing (NGS). Each sample was designed with 3 repeat samples.
2018-10-24 | GSE121700 | GEO
Project description:Transforming growth factor‐beta (TGF‐β1) plays an important regulatory role in the progression of chronic kidney failure. Further, damage to kidney glomerular mesangial cells is central to the progression of diabetic nephropathy. The aim of this study was to explore the genetic associations between mRNA, microRNA, and epigenetics in mesangial cells in response to TGF‐β1. The regulatory effects of TGF‐β1 on mesangial cells were investigated at different molecular levels by treating mesangial cells with TGF‐β1 for 3 days followed by genome‐wide miRNA, RNA, MeDIP-seq, and H3K27Me3 expression profiling using next-generation sequencing (NGS). Each sample was designed with 3 repeat samples.
2018-10-24 | GSE121687 | GEO