Transcriptome of the distal late segment of the zebrafish mesonephros
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE96519 | GEO | 2018/03/31
REPOSITORIES: GEO
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Project description:Kidney distal convoluted tubules (DCT) are important for regulation of urinary salt excretion. Aldosterone is known to exert long-term effects in this segment, and regulate sodium reabsorption via increasing abundance of the Na+-Cl- cotransporter (NCC) and the epithelial Na channel ENaC. Whether acute effects of aldosterone occur in the DCT and the potential signaling networks remain unknown. Here in this study, we aim to identify the acute aldosterone-mediated signaling (rapid effects) in the DCT.
2019-06-24 | PXD010032 | Pride
Project description:Identification of renal distal convoluted tubules enriched genes
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Project description:Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e. distal convoluted tubule (DCT) and connecting tubule (CNT) and, the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, M-oM-^AM-!ENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function. Experiment Overall Design: We examined the temporal profiles of gene expression in mouse distal nephron segments and collecting ducts. The RNA was extracted from microdissected distal convoluted tubules and connecting tubules (DCT/CNT samples) or, cortical collecting ducts (CCD samples). Animals were sacrificed for microdissection every 4 hours, i.e. at ZT0, ZT4, ZT8, ZT12, ZT16 and ZT20 (ZT M-bM-^@M-^S Zeitgeber (circadian) time, indicates time of light-on as ZT0 and time of light-off as ZT12). The microarray hybridization was performed in duplicates on two pools of RNA composed of equivalent amounts of RNA prepared from five animals at each ZT time-point.
2009-10-30 | E-GEOD-17739 | biostudies-arrayexpress
Project description:The “aldosterone paradox” is a poorly understood physiological mechanism in which increases in the hormone aldosterone either serve to stabilize blood pressure by increasing sodium-chloride (NaCl) reabsorption or to excrete potassium (K+). Under low NaCl intake, abundance and activity of the thiazide-sensitive NaCl cotransporter NCC, expressed in the distal convoluted tubule (DCT), is high, whereas it is low during high K+ intake - leading to increased delivery of NaCl to downstream segments and increased electrogenic K+ secretion. Despite a critical role in blood pressure and K+ homeostasis, little is known about the molecular alterations in the DCT during the aldosterone paradox, and how they control NCC levels. The objective of this study was to define the proteome of the DCT and how it is modified by increased circulating aldosterone levels subsequent to long-term low dietary NaCl or high K+ intake.
2021-03-30 | PXD014383 | Pride
Project description:Mutations or deletions in HNF1β cause autosomal dominant tubulointerstitial kidney disease (ADTKD)-HNF1β, a rare and heterogenous disease characterized by renal cysts and/or malformation, maturity-onset diabetes of the young, hypomagnesemia, hypokalemia and hypocalciuria. The electrolyte disturbances may develop in the distal part of the nephron, which is important for finetuning of Mg2+, Ca2+, K+ reabsorption. Moreover, this segment is a prevalent site of cyst formation in ADTKD-HNF1β patients. Therefore, we aim to study the transcriptional network directed by HNF1β in the distal part of the nephron. For this we combined HNF1β ChIP-seq and mRNA expression data to identify direct targets of HNF1β in a renal distal convoluted tubule cell line (mpkDCT).
2023-07-23 | GSE196785 | GEO
Project description:The goals of this study is to compare transcriptome profiles (RNA-seq) of zebrafish intraspinal serotonergic neurons in the injury segment and distal segments after spinal cord injury. Bulk RNA-Seq samples of ISNs from the injury area and residual segments respectively were FAC-sorted from Tg(tph2:GFP) line. Total RNA was isolated using SMART-SeqTM v4 UltraTM Low Input RNA Kit for Sequencing (Clontech). Sequencing libraries (N=5-6) were generated using NEBNext UltraTM RNA Library Prep Kit for Illumina following the manufacturer’s instructions (NEB). We mapped about 50-60 million sequence reads per sample to the zebrafish genome and identified 39,714 transcripts in the zebrafish intraspinal serotonergic neurons. Our study represents the detailed analysis of transcriptomes of zebrafish intraspinal serotonergic neurons in the injury segment and distal segments after spinal cord injury.
2021-11-08 | GSE182869 | GEO
Project description:The sympathetic nervous system (SNS) plays a central role in blood pressure regulation. Recent studies have shown that cells of the distal convoluted tubule (DCT) can be stimulated directly via the beta-adrenergic receptor resulting in activation of the NaCl cotransporter NCC. Whether these effects are mediated by the beta1- or beta2-adrenergic receptor is unclear, and the acute signaling cascades rapidly activated by beta-adrenergic receptor stimulation in the DCT are unknown. Here in this study, we aim to identify the rapid salbutamol-mediated (beta2-adrenergic receptor) signaling in the DCT by looking at global protein phosphorylation changes in the mpkDCT cells.
2021-05-17 | PXD019051 | Pride
Project description:Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF. AKI in VHL-KO mice leads to prominent HIF activation in all nephron segments, as well as to reduced serum creatinine, serum urea, tubular necrosis, and apoptosis marker caspase-3 protein. At d1 after rhabdomyolysis, when tubular injury is potentially reversible, HIF mediated protection in AKI is associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal as demonstrated by qPCR, pathway enrichment analysis and immunohistochemistry. Together, our data provide evidence for a HIF-orchestrated multi-level shift towards glycolysis as a major mechanism for protection against acute tubular injury.
2013-09-05 | GSE44925 | GEO
Project description:In multipolar vertebrate neurons, action potentials (AP) initiate close to the soma, at the axonal initial segment (AIS). Invertebrate neurons are typically unipolar with dendrites integrating directly into the axon. Where APs are initiated in the axons of invertebrate neurons is unclear. Voltage-gated sodium (NaV) channels are a functional hallmark of the AIS in vertebrates. We used an intronic MiMIC to determine the endogenous gene expression and subcellular localization of the sole NaV channel in both male and female Drosophila, para. Despite being the only NaV channel in the fly, we show that only 23 ±1% of neurons in the embryonic and larval CNS express para, while in the adult CNS para is broadly expressed. We generated a single-cell transcriptomic atlas of the whole 3rd instar larval brain to identify para expressing neurons and show that it positively correlates with markers of differentiated, actively firing neurons. Therefore only 23 ±1% of larval neurons may be capable of firing NaV-dependent APs. We then show that Para is enriched in an axonal segment, distal to the site of dendritic integration into the axon, which we named the Distal Axonal Segment (DAS). The DAS is present in multiple neuron classes in both the 3rd instar larval and adult CNS. Whole cell patch clamp electrophysiological recordings of adult CNS fly neurons are consistent with the interpretation that Nav-dependent APs originate in the DAS. Identification of the distal NaV localization in fly neurons will enable more accurate interpretation of electrophysiological recordings in invertebrates.
2020-09-29 | GSE157202 | GEO