Project description:Ten-Elven Translocation (TET) proteins oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytonsie (5hmC). Our recent work found a decline in global 5hmC level in mouse kidney insulted by ischemia reperfusion (IR). However, the genomic distribution of 5hmC in mouse kidney and its relationship with gene expression remain elusive. Here, we profiled the DNA hydroxymethylome of mouse kidney by hMeDIP-seq and revealed that 5hmC is enriched in genic regions but depleted from intergenic regions. Correlation analyses showed that 5hmC enrichment in gene body is positively associated with gene expression level in mouse kidney. Moreover, IR injury-associated genes (both up- and down-regulated genes during renal IR injury) in mouse kidney exhibit significantly higher 5hmC enrichment in their gene body regions when compared to those un-changed genes. Collectively, our study not only provides the first DNA hydroxmethylome of kidney tissues but also suggests that DNA hyper-hydroxymethylation in gene body may be a novel epigenetic mark of IR injury-associated genes. Eamination of the genome-wide distribution of 5-hydroxymethylcytosine in mouse kidney tissues
Project description:Wilms tumors are pediatric cancers thought to arise from kidney-specific stem cells. In order to identify transcriptional and epigenetic mechanisms that drive these malignant cells, we compared genomewide chromatin profiles of Wilms tumors to embryonic stem (ES) cells and normal kidney. Data represent examination of genome-wide chromatin modifications in primary Wilms tumors, fetal and mature kidney.
Project description:We report a reprogrammable mouse system in which reprogramming factor expression in vivo can be controlled temporally by treatment with doxycycline (Dox). Transient expression of reprogramming factors in vivo results in tumor development in various tissues, consisting of undifferentiated dysplastic cells. We analyzed the kidney tumors developed in reprogrammable mice for global gene expressions and DNA methylations. Reprogrammable mice at 4 weeks of age were treated with Dox for 7 days followed by the withdrawal. Seven days after the withdrawal, kidney tumors were analyzed for gene expressions and DNA methylations with microarray and RRBS method, respectively. Normal kidney tissue at the same age and ES cells were analyzed as controls. To examine the early changes of gene expressions, transgene-expressing kidney cells were FACS sorted and they are utilized for microarray analysis. Primary liver tumors in reprogrammable mice and transplanted secondary kidney tumors in the subcutaneous tissues of immnodeficient mice were also analyzed for gene expressions.
Project description:Primary objectives: The main objective of this trial is to evaluate the efficacy and safety of the medicinal product TachoSil to reduce the degree of stenosis of the ureteres in patients undergoing radical cystectomy for bladder cancer and non-malignant conditions. As TachoSil is not registered for this use, a pilot study is chosen as an initial evaluation of the use in urological surgery.
The primary measurement will be assessment of kidney function at follow up relative to kidney function at inclusion. Kidney function will be evaluated by means of intravenous renography and GFR (glomerular filtration rate). A reduction in kidney function of 10% in one side measured by renography will be regarded as indicative of ureteral stenosis and a reduction of GFR 25% will indicate bilateral reduction/stenosis. . The kidney function will be assessed by intravenous renography and Glomerular Filtration Rate (GRF) at follow up after 2-3 months and 1 year after discharge.
Primary endpoints: The primary measurement will be assessment of kidney function at follow up relative to kidney function at inclusion. Kidney function will be evaluated by means of intravenous renography and GFR (glomerular filtration rate). A reduction in kidney function of 10% in one side measured by renography will be regarded as indicative of ureteral stenosis and a reduction of GFR 25% will indicate bilateral reduction/stenosis. . The kidney function will be assessed by intravenous renography and Glomerular Filtration Rate (GRF) at follow up after 2-3 months and 1 year after discharge. These two tests are chosen for evaluation of kidney function as they are the tests with a high level of evidence. All patients with reduced kidney function shown in one or both tests will be evaluated whether the reduction is caused by stenosis or other reasons (infections etc.).
Project description:Chronic kidney disease (CKD) is a progressive condition characterized by sustained alterations in kidney structure and function. Long-term kidney fibrosis is marked by glomerulosclerosis, vascular sclerosis, and tubulointerstitial fibrosis. Therefore we investigated the therapeutic potential of BMSC-CM on RPTEC/TERT1 in a fibrotic environment. Using PAA gel platforms, we mimicked the stiffness typical of chronic kidney disease patients' kidneys.
Project description:Kidney fibrosis is the hallmark of chronic kidney disease progression, however currently no antifibrotic therapies exist. This is largely because the origin, functional heterogeneity and regulation of scar-forming cells during human kidney fibrosis remains poorly understood. Here, using single cell RNA-seq, we profiled the transcriptomes of proximal tubule and non-proximal tubule cells in healthy and fibrotic human kidneys to map the entire human kidney in an unbiased approach. This enabled mapping of all matrix-producing cells at high resolution, revealing distinct subpopulations of pericytes and fibroblasts as the major cellular sources of scar forming myofibroblasts during human kidney fibrosis. We used genetic fate-tracing, time-course single cell RNA-seq and ATAC-seq experiments in mice, and spatial transcriptomics in human kidney fibrosis to functionally interrogate these findings, shedding new light on the origin, heterogeneity and differentiation of human kidney myofibroblasts and their fibroblast and pericyte precursors at unprecedented resolution. Finally, we used this strategy to facilitate target discovery, identifying Nkd2 as a myofibroblast-specific target in human kidney fibrosis.
Project description:miRNA plays a role as post-transcriptional regulator. However, miRNAs in the kidney collecting duct cell have not been well understood. So we aimed to profile miRNAs in the kidney inner medullary collecting duct (IMCD) cells, and to identify the vasopressin-responsive miRNAs in the kidney IMCD cells. The microarray assay revealed that relative expression of miRNAs in the kidney IMCD cells was changed by desmopressin (dDAVP) stimulation.
Project description:Mutations in Bicaudaul C 1 (BICC1), evolutionary conserved RNA-binding protein, cause renal cysts in mice and humans. These renal cysts are reminiscent of Polycystic Kidney Disease (PKD). How BICC1 is involved in the pathogenesis of polycystic kidney disease is still unknown. Recent studies highlighted that HNF4A plays a role in the regulation of metabolic pathways deregulated in this renal disease. Moreover, Menezes et al. [2012, https://doi.org/10.1371/journal.pgen.1003053] showed that combined kidney inactivation of Hnf4a and Pkd1 in mice significantly worsened the cystic phenotype. Here we investigated whether the DNA binding and transcriptional activity of HNF4A might be deregulated in kidneys from Bicc1 mouse model of polycystic kidney disease. HNF4A, H3K27ac, H3K4me1 ChIPseq experiments were performed in kidneys from male and female Bicc1 WT and KO mice. From the contralateral kidneys of the same animals used for the ChIPseq experiments, the total RNA was extracted for gene expression profiling by RNAseq. The RNAseq data was used to support the ChIP-seq analysis and to reveal deregulated pathways in BICC1 mutants.
Project description:We performed CUT&RUN sequencing to characterize HNF4A binding sites in human adult kidney and kidney organoid-derived proximal tubular cells.