High 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.
No associated publication
No sample metadata fields
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.
No associated publication
No sample metadata fields
View SamplesQuantitative and qualitative analysis of small RNAs in human endothelial cells and exosomes provides insights into localized RNA processing, degradation and sorting
No associated publication
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression in the ventral tegmental area of 5 pairs of rat lines selectively bred for high or low ethanol consumption.
No sample metadata fields
View SamplesTime series of gene expression arrays before and during treatment of Hepatitis C; days 0, 1, 2, 7, 14 and 28 for 69 participants (IDs 1 through 69 are used).
Changes in gene expression during pegylated interferon and ribavirin therapy of chronic hepatitis C virus distinguish responders from nonresponders to antiviral therapy.
No sample metadata fields
View SamplesStudy of PBMC gene expression during the first 10 weeks of therapy with Pegylated-interferon-alfa2b (PegIntronTM) and ribavirin (administered by weight) in HCV patients.
Cyclic changes in gene expression induced by Peg-interferon alfa-2b plus ribavirin in peripheral blood monocytes (PBMC) of hepatitis C patients during the first 10 weeks of treatment.
Subject
View SamplesThe objective of this study was to determine common innate differences in gene expression in the nucleus accumbens shell among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats.
Gene expression in the ventral tegmental area of 5 pairs of rat lines selectively bred for high or low ethanol consumption.
No sample metadata fields
View SamplesThe objective of this study was to determine changes in gene expression within the extended amygdala following binge-like drinking by alcohol-preferring (P) rats. Adult male P rats were given 1-hr access to 15 and 30% ethanol (EtOH) three times daily for 8 weeks. Rats (n = 10/time point for EtOH and n = 6/time point for water) were killed by decapitation 1, 6 and 24 hr after the last drinking episode. Brains were extracted and rapidly frozen in isopentane in dry ice. RNA was prepared from individual micropunch samples of the nucleus accumbens shell (ACB-sh) and central nucleus of the amygada (CeA); microarray analyses were conducted with Affymetrix Rat 230.2 chips. EtOH intakes were 1.5-2 g/kg/session. Because too few genes changed at the individual time points, an overall effect, comparing the water and EtOH groups, was determined. In the ACB-sh and CeA, there were 276 and 402 probe sets for named genes, respectively, that were different between the two groups. There were 1.5- to 3.5- fold more genes up-regulated than down-regulated in both regions, with most differences between 1.1- to 1.2-fold. Although there were several significant Biological Processes categories in common between the 2 regions (e.g., synaptic transmission, neurite development), there were few genes in common between the two regions that differed between the EtOH and water groups. Overall, the results suggest that chronic binge-like alcohol drinking by P rats produces changes in the expression of genes that could alter neuronal function by different mechanisms in the ACB-sh and CeA.
Changes in gene expression in regions of the extended amygdala of alcohol-preferring rats after binge-like alcohol drinking.
Specimen part
View SamplesThe objective of this study was to determine common innate differences in gene expression in the ventral tegmental area (VTA) among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats. There were between 350 and 1400 unique named genes that were significantly different between the individual line-pairs. Gene Ontology (GO) and Ingenuity Pathways analyses indicated significant categories and networks in common for up to 3 line-pairs, but not for all 5 line-pairs; there were few genes in common between any of the line-pairs in these categories and networks. The overall ANOVAs of the combined data for the 5 line-pairs indicated over 1300 significant differences in expression of named genes. Ingenuity analysis revealed (a) several significant networks with clusters of genes associated with App, Egfr, Ccnd1, Itga2b, Rxra and Vcl; and (b) changes in genes within networks associated with dopamine, the glutamate synapse, Nfkb signaling, IL pathways and integrin. There were 22 genes that were significantly different in the overall ANOVA and were significantly different (in the direction) in at least 3 line-pairs, e.g., Crebl2, Gsta4, Itga9 & Itg2. In conclusion, the findings suggest that (a) different innate mechanisms may be contributing to vulnerability to high alcohol drinking behavior among the selectively bred lines, and (b) small contributions in expression of multiple genes within certain transmitter systems and intracellular signaling pathways may contribute to the disparate alcohol drinking characteristics of the 5 line-pairs.
Gene expression in the ventral tegmental area of 5 pairs of rat lines selectively bred for high or low ethanol consumption.
No sample metadata fields
View Samples