Human podocyte differentiation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE1545 | GEO | 2008/01/05
SECONDARY ACCESSION(S): PRJNA89941
REPOSITORIES: GEO
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Project description:Microarray analysis of the molecular phenotype of the glomerular podocyte during temperature shift-induced differentiation Keywords = glomerular podocyte Keywords = differentiation
2010-05-26 | E-GEOD-1545 | biostudies-arrayexpress
Project description:The specialized glomerular epithelial cell (podocyte) of the kidney is a complex cell that is often damaged in glomerular diseases. Study of this cell type is facilitated by an in vitro system of propagation of conditionally immortalized podocytes. Here, genes that are differentially expressed in this in vitro model of podocyte differentiation are evaluated. Conditionally immortalized undifferentiated mouse podocytes were cultured under permissive conditions at 33*C. Podocytes that were differentiated at the non-permissive conditions at 37*C were used for comparison.
2010-08-28 | E-GEOD-23856 | biostudies-arrayexpress
Project description:The specialized glomerular epithelial cell (podocyte) of the kidney is a complex cell that is often damaged in glomerular diseases. Study of this cell type is facilitated by an in vitro system of propagation of conditionally immortalized podocytes. Here, genes that are differentially expressed in this in vitro model of podocyte differentiation are evaluated.
2010-08-28 | GSE23856 | GEO
Project description:The progression of proteinuric kidney disease is associated with podocyte loss but the mechanisms remain unclear. Podocytes reenter the cell cycle to repair damaged ds DNA breaks. However, unsuccessful repair results in podocytes crossing the G1/S checkpoint and undergoes abortive cytokinesis. In this study, we identified Pfn1 as a major contributor in maintaining glomerular integrity and its loss in mice results in severe proteinuria, and kidney failure due to podocyte mitotic catastrophe, characterized by abundant multinucleated cells. Reentry of podocytes were identified by using FUCCI-2aR mice, accompanying the alteration of cell-cycle associated proteins, such as P21, P53, Cyclin B, and Cyclin D. Podocyte-specific translating ribosome affinity purification (TRAP) and RNAseq revealed a reduction of Ribosomal RNA-processing protein 8 (Rrp8) and re-expression of Rrp8 partially rescued the in-vitro phenotype. Clinical analysis of patients with proteinuric kidney disease demonstrated multinucleated podocytes and reduced podocyte profilin1 in kidney tissue. These results suggest that profilin is indispensible in regulating podocyte cell cycle and its disruption contributes to podocyte loss through mitotic catastrophe.
2023-12-01 | GSE227414 | GEO
Project description:Podocyte histone deacetylases (HDAC) are essential in maintaining a normal glomerular filtration barrier by modulating podocyte quiescence. Podocyte-specific loss Hdac1 and 2 in mice results in severe proteinuria and sustained DNA damage, likely caused by epigenetic alterations and deficient DNA repair, that result in podocyte senescence. Through glomeruli isolation and RNA-seq profiling from the mutant mice, we demonstrated that senescent podocytes develop a senescence-associated secretory phenotype (SASP) that contribute to the loss of podocytes. The role of HDACs in senescence may provide important clues in our understanding of how podocytes are lost following injury.
2022-10-25 | GSE216088 | GEO
Project description:Overexpression of glomerular JAK2 mRNA specifically in glomerular podocytes of 129S6 mice led to significant increases in albuminuria, mesangial expansion, glomerulosclerosis, glomerular fibronectin accumulation, and glomerular basement membrane thickening as well as a significant reduction in podocyte density in diabetic mice. Treatment with a specific JAK1/2 inhibitor partly reversed the major phenotypic changes of DKD
2017-07-31 | GSE86317 | GEO
Project description:Nephrotic syndrome (NS) occurs when the glomerular filtration barrier becomes excessively permeable leading to massive proteinuria. In childhood NS, dysregulation of the immune system has been implicated and increasing evidence points to the central role of podocytes in the pathogenesis. Children with NS are typically treated with an empiric course of glucocorticoid (Gc) therapy; a class of steroids that are activating ligands for the glucocorticoid receptor (GR) transcription factor. Although Gc-therapy has been the cornerstone of NS management for decades, the mechanism of action, and target cell, remain poorly understood. We tested the hypothesis that Gc acts directly on the podocyte to produce clinically useful effects without involvement of the immune system. In human podocytes, we demonstrated that the basic GR-signalling mechanism is intact and that Gc induced an increase in podocyte barrier function. To gain mechanistic insight we performed RNA microarray and ChIP-sequencing and identified Gc regulation of motility genes.
2017-07-17 | E-MTAB-5235 | biostudies-arrayexpress
Project description:Podocyte injury is the hallmark of proteinuric kidney diseases, such as Focal Segmental Glomerulosclerosis and Minimal Change Disease. Therapeutic strategies in the management of proteinuric diseases are limited. Although agents such as glucocorticoids, cyclosporine, and rituximab have direct effects on the podocyte by stabilizing its actin cytoskeleton, these drugs are riddled with systemic toxicity and off-target effects that hinder their chronic use. We previously demonstrated that the loss of the kidney-enriched zinc finger transcription factor, Krüppel-like factor 15 (KLF15), increases susceptibility to proteinuric kidney disease as well as attenuates the salutary effects of retinoic acid and glucocorticoids in the podocyte. Here, we show that podocyte-specific induction of KLF15, using the tetracycline-inducible system, attenuated podocyte injury, glomerulosclerosis, tubulointerstitial fibrosis and inflammation, while improving renal function and overall survival in HIV-1 transgenic mice. Enrichment analysis of mRNA sequencing of isolated glomerular extracts from this model shows that podocyte-specific induction of KLF15 activates pathways involved in stabilization of actin cytoskeleton, focal adhesion, and podocyte differentiation. Transcription factor enrichment analysis, with further experimental validation, suggests that KLF15 activity is in part mediated by Wilms Tumor 1 (WT1), a transcription factor known to be critical for podocyte differentiation. Further, we confirmed the benefits of podocyte-specific induction of KLF15 in the adriamycin-induced proteinuric murine model. Collectively, these observations suggest that induction of KLF15 might be a potential therapeutic target in the treatment of proteinuric kidney disease.
2018-08-02 | GSE117987 | GEO
Project description:Glomerular podocytes are highly differentiated kidney cells that constitute one of the key components responsible for removing toxins and metabolic waste while preserving nutrients in the bloodstream in the renal glomerulus. In addition, podocytes contribute significantly to the formation of the glomerular basement membrane and the integrity of the vascular endothelium. Thus, podocyte injury and/or loss of podocytes results in impaired blood filtration and causes many common renal diseases characterized by severe proteinuria (protein in the urine) and hypoalbuminemia (low levels of blood albumin). Small lipopholic molecules such as steroids, fatty acids, prostaglandins and vitamin metabolites control many aspects of animal development, cell proliferation and differentiation, and homeostasis through binding to their intracellular receptors. Upon binding to their cognate ligands, these nuclear receptors (NRs) are capable of turning on or off of an array of gene networks. By doing so, they regulate a whole spectrum of cellular activities. The ability of small molecule hormones to regulate NR activity makes them excellent pharmaceutical targets. Clinical evidence and animal studies have implicated several NRs in contributing to podocyte development and disease. Recent studies from animals and cultured human or mouse podocytes indicate that synthetic hormones including estradiol, glucocorticoid, retinoid, pioglitazone, vitamin D3 and WY-14643 protect or rescue podocytes from experimental injury. Post treatment of injured podocytes with ligands for the above-mentioned NRs restores cytoskeletal architecture of the podocytes. Nonetheless, the mechanisms underlying the ability of these hormones in protecting podocytes remain largely unexplored. This is partly due to our limited knowledge of the target genes controlled by these hormones. In order to elucidate the mechanisms by which Dex, VD3 and ATRA elicit their renoprotective activity, we initiate a gene expression profiling study to identify the target genes of these hormones in cultured human podocytes. The temperature-sensitive cultured human podocytes (HPCs) were maintained in culture media of RPMI supplemented with 10% FBS, 1% antibiotics and the Insulin-Transferrin-Selenium at the permissive (undifferentiated) temperature of 33 Celsius degree. The 70%~80% confluent HPCs were induced to in vitro differentiate by culturing at 37 Celsius degree for 2 days then with incubation of vehicle (equal volume of DMSO), 100 nM all-trans retinoic acid (ATRA), 100 nM dexamethasone (Dex), or 100 nM vitamin D3 (VD3) treatment for 3 more days. The undifferentiated HPCs with vehicle (equal volume of DMSO) treatment was included as a control. The total RNAs of these cells were isolated using USB prepEase RNA spin kit following the manufacturer's instructions. Total 1 microgram RNA at 100 nanogram per microliter for each sample were sent for a single-channel gene expression microarray studies using HumanRef-8 chip (V3_0_R3_11282963) on Illumina BeadStation platform. The RNA were converted to aRNA and appropriately labelled using MessageAmp Biotin aRNA Amplification Kit (Ambion) following the manufacturer's instructions. The raw data were collected by scanning the chip on Illumina BeadStation. Background subtracted raw data were exported and the following analysis was done in R/Bioconductor environment. Thus, we were able to compare the gene expression profiles between differentiated and undifferentiated HPCs with or without hormone treatment.
2013-05-30 | E-GEOD-39823 | biostudies-arrayexpress
Project description:Podocyte injury in diabetic kidney disease contributes to the development of albuminuria and subsequent renal decline. Clinically, gastric bypass surgery is associated with reductions in albuminuria, and rodent studies demonstrate coherent improvements in renal histology. We aimed to investigate the mechanisms underpinning remission of albuminuria following gastric bypass focussing on podocyte injury. Firstly, we tracked the evolution of albuminuria and cognate evidence of histological and ultrastructural damage to the glomerulus in male Zucker Diabetic Fatty rats. Secondly, we examined the impact of gastric bypass in these rats, focussing on podocyte injury. Thirdly, we conducted a global transcriptomic study profiling the shift in the renal transcriptome in the Zucker Diabetic Fatty rats rat and its relevance to human disease. Lastly, we explored whether gastric bypass could reverse the changes seen in the disease associated transcriptome. Albuminuria in the Zucker Diabetic Fatty rat developed by 12 weeks of age. This was accompanied by glomerulomegaly, podocyte stress and ultrastructural evidence of podocyte dedifferentiation. When animals underwent gastric bypass at 12 weeks of age, marked reductions in albuminuria in association with normalisation of glomerular tuft size, attenuation of podocyte stress and improvements in podocyte foot process morphology were observed within 2 months of surgery. A characteristic disease associated gene expression signature was observed in the kidneys of Zucker Diabetic Fatty rats, with a core set of alterations conserved in global analysis of the human DKD transcriptome. Many of the shared gene expression alterations were reversed by gastric bypass. Reductions in podocyte injury represent a key mechanism underpinning the remission of albuminuria following gastric bypass.
2019-07-10 | GSE117085 | GEO