Project description:Transcriptome comparison of glomeruli from kidneys with focal segmental glomerulosclerosis (FSGS) and glomeruli from the unaffected portion of tumor nephrectomies. High-density Affymetrix Human Transcriptome Arrays (HTA) 2.0 were used for the gene expression analysis.
Project description:Transcriptome comparison of tubular tissues from kidneys with focal segmental glomerulosclerosis (FSGS) and tubular tissues from the unaffected portion of tumor nephrectomies. High-density Affymetrix Human Transcriptome Arrays (HTA) 2.0 were used for the gene expression analysis.
Project description:Transcriptome comparison of tubulointerstitial tissues from kidneys with focal segmental glomerulosclerosis (FSGS) and tubulointerstitial tissues from the unaffected portion of surgical nephrectomies. High-density Affymetrix Human Transcriptome Arrays (HTA) 2.0 were used for the gene expression analysis.
Project description:To search for biomarkers to differentiate Adult-Onset Steroid Sensitive focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Compared the profiles of glomerular transcriptomes between patients with FSGS and patients with MCD using microarray analysis. This dataset is part of the TransQST collection.
Project description:Transcriptome comparison of glomeruli from kidneys with FSGS and glomeruli from the unaffected portion of tumor nephrectomies. This study aims to investigate the pathogenesis and the mechanism of FSGS
Project description:We performed a genomewide differential gene expression analysis by Ion AmpliSeqTM Transcriptome sequencing that targets more than 20,000 human genes to gain insights into the genes and pathways involved in the onset of familial steroid-resistant Focal Segmental Glomerulosclerosis (FSGS) driven by the presence of a heterozygous mutation in the PAX2 gene (PAX2G189R/+). Using a stepwise protocol, we differentiated control and PAX2G189R/+ induced pluripotent stem cells into podocytes and we performed whole-transcriptomic analysis on control and patient cells on days 6, 13 and 18 of differentiation. Our data indicated that the PAX2 mutation mainly affects the focal adhesion pathway and the expression of IGF1, a PAX2 target, in adult podocytes that are more susceptible to cell death by environmental triggers.
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.
Project description:Parietal epithelial cells (PECs) are part of renal progenitor cells with similarities to bone marrow stem cell niche. In focal segmental glomerulosclerosis (FSGS) PECs become activated and contribute to extracellular matrix deposition. Colony stimulating factor-1 (CSF-1), a hematopoietic growth factor, acts via its specific receptor, CSF-1R, and has been implicated in several glomerular diseases, although its role on PEC activation is unknown. We found that CSF-1R was upregulated in PECs and podocytes from human biopsies with FSGS. Through in vitro studies, we demonstrated that PECs constitutively express CSF-1R. Incubation with CSF-1 induced CSF-1R upregulation and significant transcriptional regulation of genes involved in pathways associated with PEC activation. Specifically, CSF-1/CSF-1R activated the ERK1/2 pathway and upregulated CD44 in PECs, while both ERK and CSF-1R inhibitors reduced CD44 expression. Our functional studies showed that CSF-1 induced PEC proliferation and migration, while reducing the differentiation of PECs into podocytes. These results were validated in the Adriamycin-induced FSGS experimental model. Importantly, treatment with either the CSF-1R-specific inhibitor GW2580 or Ki20227 provided a robust therapeutic effect. In conclusion, we provide the first evidence of the role of the CSF-1/CSF-1R pathway in PEC activation in FSGS, paving the way for future clinical studies investigating the therapeutic effect of CSF-1R inhibitors on FSGS in humans.