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Genome-wide chromatin accessibility and gene expression profiling of renal cell carcinoma and matched normal kidney tubules [DNase-seq]

ABSTRACT: Genome-wide chromatin accessibility and gene expression profiling of renal cell carcinoma and matched normal kidney tubules [DNase-seq]

PROVIDER: PRJNA481762 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7537350_1.fastq.gz	Fastqsanger.gz
	SRR7537350_2.fastq.gz	Fastqsanger.gz
	SRR7537360_1.fastq.gz	Fastqsanger.gz
	SRR7537360_2.fastq.gz	Fastqsanger.gz
	SRR7537351_1.fastq.gz	Fastqsanger.gz

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Genome-wide chromatin accessibility and gene expression profiling of renal cell carcinoma and matched normal kidney tubules [DNase-seq]

Project description:We generated primary cultures from renal cell carcinoma and matched normal primary kidney cortex tubule cell cultures from 3 patients. Early passage cultures of these two cell types were subjected to chromatin accessibility profiling (DNase-seq) and gene expression profiling (RNA-seq). Studying these paired and patient-matched controlled data sets will shed light on the epigenomic changes that underlie transformation of kidney tubules into malignant cancers.

2018-07-19 | GSE117323 | GEO

Genome-wide chromatin accessibility and gene expression profiling of renal cell carcinoma and matched normal kidney tubules [RNA-Seq]

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Genome-wide chromatin accessibility and gene expression profiling of renal cell carcinoma and matched normal kidney tubules [RNA-Seq]

Project description:Genome-wide chromatin accessibility and gene expression profiling of renal cell carcinoma and matched normal kidney tubules [RNA-Seq]

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PPARs and c-Myc regulate metabolism of renal tubules

Project description:Different segments of renal tubules have distinct metabolic features and functions, and defective metabolism in renal tubules is involved in the pathobiology of kidney diseases. However, the mechanisms underlying the metabolic regulation in renal tubules remain to be defined. We demonstrated that the renal proximal tubule (PT) has high expression of fatty acid and lipid metabolism enzymes, which is transcriptionally upregulated by abundantly expressed peroxisome proliferator-activated receptor (PPAR)/γ to support active lipid metabolism. In contrast, the renal distal tubule (DT) has elevated glycolytic enzyme expression corresponding with high rates of glycolysis, and this increased expression is mediated by abundantly expressed c-Myc. In addition, Nrf2 upregulated glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-dependent malic enzyme 1 expression for NADPH production and antioxidation in the DT. Highly expressed PPARγ transcriptionally enhanced expression of the protease iRhom2 in the PT, which suppressed epidermal growth factor (EGF) expression and secretion, inhibiting EGF receptor activation-dependent glycolytic gene expression and maintaining the low level of glycolysis. PPARγ inhibition reduced iRhom2 expression and increased EGF and GLUT1 expression in the PT in mice, resulting in hypertrophy of renal tubules and inhibited kidney functions, which can be rescued by inhibition of glycolysis via treatment with 2-deoxy-D-glucose. These findings delineate instrumental molecular mechanisms underlying the active lipid metabolism and suppressed glycolysis in the PT and active glycolysis in the DT and reveal critical roles for PPARs and c-Myc in maintaining metabolic homeostasis in the kidney

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Immunohistochemical Investigation for Renal Tubules in Adaptive and Maladaptive Repair Process after Renal Tubular Injury in the Kidney of Rats

Project description:Acute kidney injury (AKI) have been thought to be reversible condition, however, emerging evidence demonstrated association between AKI and subsequent development of irreversible fibrosis and chronic kidney disease. In the present study, since recovery of AKI depends on renal tubular regeneration, factors expressing in renal tubules in adaptive or maladaptive repair process were investigated to predict reversibility of kidney injury. In the kidney of female F344 rats subjected to ischemia/reperfusion (I/R), regenerative tubules and dilated tubules were observed at 3 and 7 days after I/R. In fibrotic areas of the kidney of male SD rats subjected to I/R, renal tubules were dilated or atrophied. From microarray data of regenerative tubules, survivin, sex-determining region Y (SRY)-box 9 (SOX9), and CD44 were extracted as factors possibly relating to tubular regeneration or fibrosis. Immunohistochmical analysis demonstrated that survivin and SOX9 expressed in regenerative tubules, while SOX9 also expressed in renal tubules in fibrotic area, indicating that survivin and SOX9 contribute renal tubular regeneration, but sustained SOX9 expression may lead fibrosis. CD44 expressed in dilated tubules at day 3 and 7, and tubules in fibrotic area, suggesting that CD44 expressed in maladaptive tubules. These information will be helpful to consider reversibility of kidney injury.

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