Quantitative and qualitative analysis of small RNAs in human endothelial cells and exosomes provides insights into localized RNA processing, degradation and sorting
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View SamplesIn chronic kidney disease (CKD) state, various changes in gene expression in kidneys are occurring, reflecting accumulation of uremic toxins, local inflammation, increased oxidative stress, and up-regulation of pro-fibrotic signals. However, little studies have been conducted for comprehensive evaluation of transcriptomic changes in CKD kidneys. Identification of key signals in CKD may lead to the elucidation of the mechanism of CKD progression and the development of therapeutic methods.
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View SamplesHigh serum concentrations of kidney-derived protein uromodulin (Tamm-Horsfall protein or THP) have recently been shown to be independently associated with low mortality in both older adults and cardiac patients, but the underlying mechanism remains unclear. Here, we show that THP inhibits the generation of reactive oxygen species (ROS) both in the kidney and systemically. Consistent with this experimental data, the concentration of circulating THP in patients with surgery-induced acute kidney injury (AKI) correlated with systemic oxidative damage. THP in the serum dropped after AKI, and was associated with an increase in systemic ROS. The increase in oxidant injury correlated with post-surgical mortality and need for dialysis. Mechanistically, THP inhibited the activation of the TRPM2 channel. Furthermore, inhibition of TRPM2 in vivo in a mouse model, mitigated the systemic increase in ROS during AKI and THP deficiency. Our results suggest that THP is a key regulator of systemic oxidative stress by suppressing TRPM2 activity and our findings might help to explain how circulating THP deficiency is linked with poor outcomes and increased mortality.
Circulating uromodulin inhibits systemic oxidative stress by inactivating the TRPM2 channel.
Specimen part
View SamplesHypoxia plays important roles in progression of chronic kidney diseases. HIF1 (hypoxia inducible factor 1) is a master transcriptional factor under hypoxic condition. To clarify the molecular mechanisms of HIF1 and identify novel linc RNAs under hypoxia, we performed RNA-seq using human renal proximal tubular epithelial cells (RPTEC). In addition, we use Dznep which is an inhibitor of H3K27me3 to examine the relationship between HIF1 and epigenetic modifiers under hypoxia.
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View SamplesHypoxia plays important roles in progression of chronic kidney diseases. HIF1 (hypoxia inducible factor 1) is a master transcriptional factor under hypoxic condition. To clarify the molecular mechanisms of HIF1 and identify novel lincRNAs under hypoxia, we performed RNA-seq using human renal proximal tubular cells (HK2: human kidney-2). In addition, we use Dznep which is an inhibitor of H3K27me3 to examine the relationship between HIF1 and epigenetic modifiers under hypoxia.
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View SamplesThe study aimed to investigate genome-wide transcriptome changes in response to L-lactate in primary neuron cultures.
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Sex, Specimen part, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
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Sex, Specimen part
View SamplesSkin is the largest organ in the body and serves important barrier, regulatory, and sensory functions. Like other tissues, skin is subject to temporal fluctuations in physiological responses under both homeostatic and stressed states. To gain insight into these fluctuations, we investigated the role of the circadian clock in the transcriptional regulation of skin
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Sex, Specimen part
View SamplesSkin is the largest organ in the body and serves important barrier, regulatory, and sensory functions. Like other tissues, skin is subject to temporal fluctuations in physiological responses under both homeostatic and stressed states. To gain insight into these fluctuations, we investigated the role of the circadian clock in the transcriptional regulation of skin
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Sex, Specimen part
View SamplesPosttraumatic stress disorder (PTSD) has been linked to immunologic dysregulation. Gene expression profiling has emerged as a promising tool for understanding the pathophysiology of PTSD. However, to date, all but one gene expression study was based on whole blood or unsorted peripheral blood mononuclear cell (PBMC), a complex tissue consisting of several populations of cells. The objective of this study was to utilize RNA sequencing to simultaneously profile the gene-expression of four immune cell subpopulations in World Trade Center responders. Pathway analyses identified gene sets related to immune response and inflammation as being among the differentially expressed genes in PTSD, including mast cell activation and regulation in CD4T, interferon-beta production in CD8T, and neutrophil related gene sets in monocytes. These findings are suggestive that immune cell dysregulation involves gene expression in various cell populations.
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