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:Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are patterns of kidney injury observed in the filtering units of the kidney known as glomeruli. From the NURTuRE cohort of individuals with nephrotic syndrome (NS), we performed laser microdissection and mass spectrometry analysis of kidney biopsy samples to identify proteomic patterns of disease. 56 individuals with idiopathic NS segregated by histological pattern (37 MCD and 19 FSGS) across three age groups: early childhood (0-6 years), late childhood (6-18 years) and adult (>18 years). We identified global differences in glomerular cell and extracellular matrix composition related to both histological pattern and age.
Project description:We profiled manually microdissected tubulointerstitial tissue from 43 IgA nephropathy, 3 diabetes mellitus nephropathy, 3 focal segmental glomerulosclerosis, 3 lupus nephritis, 4 membranous nephropathy, and 9 minimal change disease biopsy cores and 22 nephrectomy controls by RNA sequencing. The 3 outliers which were not included in our main analysis were also uploaded in this database.
Project description:Podocyte injury is the hallmark of both focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) and is ultimately reflected in foot process effacement proteinuria. Triggers and pathogenic pathways leading to podocyte cytoskeleton rearrangements are however incompletely explained. Here, we aimed to contribute to the understanding of these pathways using tissue bottom-up proteomic profiling of laser capture micro dissected glomeruli from MCD and 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:Regulated intracellular proteolysis is essential in maintaining the integrity of podocytes and the glomerular filtration barrier of the kidney. Altered proteolytic substrate turnover has been associated with various glomerular diseases ranging from diabetic nephropathy to focal and segmental glomerulosclerosis. However, thus far it has not been possible to systematically identify proteolytically cleaved proteins although some of the proteases have been characterized. Here we applied TAILS to identify N-termini in rat glomeruli and their changes on PAN-induced injury.
Project description:DNA repair is essential for preserving genome integrity. Podocytes, post-mitotic epithelial cells of the kidney filtration unit, bear limited regenerative capacity, yet their survival is indispensable for kidney health. Podocyte loss is a hallmark of the aging process and of many diseases, but the underlying factors remain unclear. We investigated the consequences of DNA damage in a podocyte-specific knockout mouse model for Ercc1 and in cultured podocytes under genomic stress. Furthermore, we characterized DNA damage-related alterations in mouse and human renal tissue of different ages and patients suffering from minimal change disease and focal segmental glomerulosclerosis. Ercc1 knockout resulted in accumulation of DNA damage ensuing albuminuria and kidney disease. Podocytes reacted to genomic stress by activating mTORC1 signaling in vitro and in vivo. Perturbed DNA repair gene expression and genomic stress in podocytes was also detected in focal segmental glomerulosclerosis. Beyond that, DNA damage signaling occurred in podocytes of healthy aging mice and humans. We provide evidence that genome maintenance in podocytes is linked to the mTORC1 pathway, involved in the aging process and the development of glomerulosclerosis.
Project description:Regulated intracellular proteolysis is essential in maintaining the integrity of podocytes and the glomerular filtration barrier of the kidney. Altered proteolytic substrate turnover has been associated with various glomerular diseases ranging from diabetic nephropathy to focal and segmental glomerulosclerosis. However, thus far it has not been possible to systematically identify proteolytically cleaved proteins although some of the proteases have been characterized. Here we applied TAILS to map N-termini in the mouse glomeruli proteome and to determine and quantify N termini in podocyte cell cultures challenged with PAN.
Project description:Regulated intracellular proteolysis is essential in maintaining the integrity of podocytes and the glomerular filtration barrier of the kidney. Altered proteolytic substrate turnover has been associated with various glomerular diseases ranging from diabetic nephropathy to focal and segmental glomerulosclerosis. However, thus far it has not been possible to systematically identify proteolytically cleaved proteins although some of the proteases have been characterized. Here we applied TAILS to map N-termini in the mouse glomeruli proteome and to determine and quantify N termini in podocyte cell cultures challenged with PAN.
