Bulk-RNAseq data of podocytes treated with FSGS sera
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ABSTRACT:
PROVIDER: PRJEB83086 | ENA |
REPOSITORIES: ENA
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Project description:Human immortalised podocytes were exposed to 10% sera from a patient with focal segmental glomerulosclerosis when they were presenting with disease, on weekly vincristine treatment, and in remission. RNA was extracted with the Qiagen RNEasy plus kit, purity and concentration were assessed by nanodrop. The library was prepped with KAPA mRNA HyperPrep Kit and paired-end sequenced with an average of 16 million reads per sample on the Illumina NextSeq 2000 platform. Numbers at the beginning refer to biological repeat (sequential passage of cells). AP - acute presentation; OT - on vincristine treatment; R - Remission.
2024-12-31 | E-MTAB-14604 | biostudies-arrayexpress
Project description:Focal segmental glomerulosclerosis (FSGS) is characterized by damage to podocytes, a crucial pathological feature. While several mechanisms of podocyte injury have been suggested, many questions remain unanswered. Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2), a serine/threonine kinase with diverse cellular functions, appears to play a significant role. We observed activation of ROCK2 in podocytes of mice with FSGS induced by adriamycin (ADR), as well as in cultured podocytes exposed to ADR. To delve deeper, we used conditional knockout mice where the ROCK2 gene was specifically disrupted in podocytes (PR2KO). These mice showed resistance to ADR-induced albuminuria, glomerular sclerosis, and podocyte damage. Additionally, pharmacological inhibition of ROCK2 significantly improved podocyte loss and kidney sclerosis in a mouse model of FSGS by counteracting profibrotic factors. RNA sequencing of podocytes treated with a ROCK2 inhibitor confirmed ROCK2's role as a regulator of the cyclic nucleotide signaling pathway. Our findings underscore the potential of ROCK2 inhibition as a therapeutic avenue for FSGS.
2024-03-20 | GSE262013 | GEO
Project description:Recurrence of focal segmental glomerulosclerosis (rFSGS) after kidney transplantation is a cause of early and accelerated graft loss. Immuneadsorption can alleviate renal dysfunction and suggests that circulating antibodies (Ab) are likely implicated in disease pathogenesis. To evaluate pathogenic Ab in rFSGS, we processed 141 unique serum samples from patients with and without primary rFSGS (n=64) and 34 non-FSGS control, transplanted at five (US and EU) hospitals. 9000 antigens were screened in pre-transplant sera by protein arrays and 10 Ab targeting glomerular antigens were selected for ELISA validation. A panel of 7 Ab (CD40, PTPRO, CGB-5, FAS, P2RY11, SNRPB2 and APOL2) could predict post-transplant FSGS recurrence with 92% accuracy. Pre-transplant elevation of anti-CD40 Ab levels alone had a substantial impact (78% accuracy) on the identification of rFSGS risk after transplantation. Epitope mapping of CD40 with customized peptide arrays and rFSGS sera demonstrated altered immunogenicity of the extracellular CD40 domain in rFSGS. Immunohistochemistry of CD40 demonstrated a differential expression of these antigens in FSGS compared to non-FSGS. Anti-CD40 Ab purified from rFSGS patients were uniquely pathogenic in human podocyte cultures; injection of these Ab resulted in heightened proteinuria, independently and in combination with suPAR in a rodent model, abrogated by injection of monoclonal Ab to CD40. In conclusion, a panel of 7 Ab can identify primary FSGS patients at high risk of recurrence prior to transplantation, allowing for customized therapies and improved patient selection for transplant. Intra-renal CD40 is an important axis of disease pathogenesis, and human trials of anti-CD40 therapies are warranted to evaluate their efficacy in preventing rFSGS and improving graft survival. The purpose of the study was to identify potential auto-Abs associated with rFSGS. We used a discovery set of pre-transplant sera from 20 unique patients with biopsy confirmed diagnosis of primary FSGS as their cause of ESRD, of which 10 had progressed to rFSGS within the first post-transplant year and 10 did not have recurrence of proteinuria or histological disease after transplantation (nrFSGS).
2014-11-04 | E-GEOD-57099 | biostudies-arrayexpress
Project description:Podocytes are crucial for the establishment and maintenance of the blood-urine filtration barrier in the glomeruli of the kidney. Activation of the Hippo signaling pathway in podocytes leads to the induction of apoptosis and could be linked to the pathogenesis of proteinuric diseases like focal segmental glomerulosclerosis (FSGS). To investigate the Hippo signaling controlled gene transcription, podocytes overexpressing LATS2, a core kinase of the Hippo pathway, were analyzed via RNA sequencing.
2018-08-30 | GSE114987 | GEO
Project description:Recurrence of focal segmental glomerulosclerosis (rFSGS) after kidney transplantation is a cause of early and accelerated graft loss. Immuneadsorption can alleviate renal dysfunction and suggests that circulating antibodies (Ab) are likely implicated in disease pathogenesis. To evaluate pathogenic Ab in rFSGS, we processed 141 unique serum samples from patients with and without primary rFSGS (n=64) and 34 non-FSGS control, transplanted at five (US and EU) hospitals. 9000 antigens were screened in pre-transplant sera by protein arrays and 10 Ab targeting glomerular antigens were selected for ELISA validation. A panel of 7 Ab (CD40, PTPRO, CGB-5, FAS, P2RY11, SNRPB2 and APOL2) could predict post-transplant FSGS recurrence with 92% accuracy. Pre-transplant elevation of anti-CD40 Ab levels alone had a substantial impact (78% accuracy) on the identification of rFSGS risk after transplantation. Epitope mapping of CD40 with customized peptide arrays and rFSGS sera demonstrated altered immunogenicity of the extracellular CD40 domain in rFSGS. Immunohistochemistry of CD40 demonstrated a differential expression of these antigens in FSGS compared to non-FSGS. Anti-CD40 Ab purified from rFSGS patients were uniquely pathogenic in human podocyte cultures; injection of these Ab resulted in heightened proteinuria, independently and in combination with suPAR in a rodent model, abrogated by injection of monoclonal Ab to CD40. In conclusion, a panel of 7 Ab can identify primary FSGS patients at high risk of recurrence prior to transplantation, allowing for customized therapies and improved patient selection for transplant. Intra-renal CD40 is an important axis of disease pathogenesis, and human trials of anti-CD40 therapies are warranted to evaluate their efficacy in preventing rFSGS and improving graft survival.
2014-11-04 | GSE57099 | GEO
Project description:Background: Many patients with idiopathic focal segmental glomerulosclerosis (FSGS) develop recurrence of proteinuria after kidney transplantation. Several circulating permeability factors (CPFs) responsible for recurrence have been suggested, but there is no consensus about the identity of CPFs in FSGS. We aimed to find proteins involved in the mechanism of action of the CPF(s) and/or potential biomarkers for the presence of CPF(s). Methods: Cultured human podocytes were exposed to plasma from patients with FSGS with presumed CPF(s), or from (disease) controls. Podocyte proteomes were analyzed by mass spectrometry and differentially expressed proteins were validated using flow cytometry, RT-PCR, and immunofluorescence. Changes in podocyte granularity were examined using flow cytometry, electron microscopy imaging and BODIPY staining. Results: Perilipin-2 protein expression was increased in podocytes exposed to presumed CPF-containing plasmas, which was related to disease state and capacity of plasma to induce granularity in podocytes. Elevated perilipin-2 levels were confirmed at protein and mRNA level. The granules observed in podocytes actually are lipid droplets. Importantly, increased perilipin-2 staining was also detected in glomeruli of the FSGS patients whose active disease plasmas induced lipid droplets in podocytes. Conclusions: Our study demonstrates that presumably CPF-containing plasma from FSGS patients alter podocyte lipid metabolism and increase perilipin-2 protein and lipid droplet accumulation. Future research should address the mechanism underlying CPF-induced alterations in podocyte lipid metabolism in the context of the pathogenesis of (recurrent) FSGS, which ultimately may result in novel leads for treatment.
2022-12-22 | PXD028536 | Pride
Project description:The diagnosis of focal segmental glomerulosclerosis (FSGS) requires a renal biopsy which is invasive and can be problematic in children and in some adults. We used single cell RNA-sequencing to explore disease-related cellular signatures in 17 urine samples from 12 FSGS subjects. We identified immune cells in urine predominantly monocytes and renal epithelial cells including podocytes. Analysis revealed M1 and M2 monocyte subsets and podocytes showing increased expression of genes involved in epithelial-to-mesenchymal transition (EMT). We confirmed M1 and M2 gene signatures using published monocyte/macrophage data from lupus nephritis and cancer. Using renal transcriptomic data from the Nephrotic Syndrome Study Network (NEPTUNE) we found that urine immune and EMT signature genes also showed higher expression in FSGS biopsies compared to minimal change disease biopsies. These results suggest that urine cell profiling may serve as a diagnostic and prognostic tool in nephrotic syndrome and may assist in identifying novel biomarkers and developing personalized therapeutic strategies.
2021-12-07 | GSE176465 | GEO
Project description:Mycophenolic Acid (MPA) is the active component of the immunosuppressant Mycophenolate Mofetil, a potent inhibitor of the inosine monophosphate dehydrogenase. Direct effects of MPA on podocytes remain largely unknown. In order to elucidate genes and pathways affected by the drug, cultured murine podocytes exposed to MPA were subjected to RNA sequencing (RNASeq) analysis. Untreated samples served as controls. The RNASeq of MPA treated podocytes identified 351 significantly affected genes (padj < 0.05; 130 downregulated / 221 upregulated). Gene Ontology-Term enrichment analysis outlined two major groups of terms of particular interest, namely actin associated terms and terms related to inflammatory cell death. In conclusion, MPA treatment has a substantial effect on the transcriptome of podocytes. Analysis of the sequencing data revealed several non-immune cell dependent areas in which MPA possibly has a favorable effect on podocytes.
2023-03-27 | E-MTAB-11702 | biostudies-arrayexpress