Adipose Angiotensin AT2 Receptors Modulate Thermogenesis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE77214 | GEO | 2016/12/07
SECONDARY ACCESSION(S): PRJNA309715
REPOSITORIES: GEO
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Project description:The human placental renin-angiotensin system (RAS) genes encoding for prorenin (REN), angiotensinogen (AGT), prorenin receptor (ATP6AP2) and angiotensin II type I (AGTR1) receptor are upregulated in early gestation and affect placental development. At this time, the placental oxygen tension is at its lowest (1-3%). Some miRNAs predicted to target the RAS are downregulated in early gestation. Our hypothesis is that the low oxygen tension in early pregnancy suppresses expression of miRNAs that target the placental RAS; thus expression of these RAS genes are upregulated. Ten miRNAs predicted to target RAS mRNAs were downregulated in response to 1% vs. 20% oxygen, and six miRNAs were decreased in cells cultured in 1% vs. 5% oxygen.
2018-11-30 | GSE121593 | GEO
Project description:The postnatal development of the mouse is characterized by a stress hyporesponsive period (SHRP), where basal corticosterone levels are low and responsiveness to mild stressors is reduced. Maternal separation is able to disrupt the SHRP and is widely used to model early trauma. In this study we aimed at identifying of brain systems involved in acute and possible long-term effects of maternal separation. We conducted a microarray-based gene expression analysis in the hypothalamic paraventricular nucleus after maternal separation, which revealed 52 differently regulated genes compared to undisturbed controls, among them are 37 up-regulated and 15 down-regulated genes. One of the prominently unregulated genes, angiotensinogen, was validated using a in-situ hybridization. Angiotensinogen is the precursor of angiotensin II the main effector of the brain renin-angiotensin system (RAS), which is known to be involved in stress system modulation in adult animals. Using the selective angiotensin type I receptor (AT(1)) antagonist candesartan we found strong effects on CRH and GR mRNA expression in the brain and ACTH release following maternal separation. AT(1) receptor blockade appears to enhance central effects of maternal separation in the neonate, suggesting a suppressing function of brain RAS during the SHRP. Taken together, our results illustrate the molecular adaptations that occur in the paraventricular nucleus following maternal separation and identify signaling cascades, that control stress system activity in the neonate. Keywords: phenotype Litters were randomly assigned to either a maternally non-separated or 24 hour maternally separated condition. At the time of testing, all pups from a litter were sacrificed immediately by decapitation.
2010-05-16 | E-GEOD-14687 | biostudies-arrayexpress
Project description:The postnatal development of the mouse is characterized by a stress hyporesponsive period (SHRP), where basal corticosterone levels are low and responsiveness to mild stressors is reduced. Maternal separation is able to disrupt the SHRP and is widely used to model early trauma. In this study we aimed at identifying of brain systems involved in acute and possible long-term effects of maternal separation. We conducted a microarray-based gene expression analysis in the hypothalamic paraventricular nucleus after maternal separation, which revealed 52 differently regulated genes compared to undisturbed controls, among them are 37 up-regulated and 15 down-regulated genes. One of the prominently unregulated genes, angiotensinogen, was validated using a in-situ hybridization. Angiotensinogen is the precursor of angiotensin II the main effector of the brain renin-angiotensin system (RAS), which is known to be involved in stress system modulation in adult animals. Using the selective angiotensin type I receptor (AT(1)) antagonist candesartan we found strong effects on CRH and GR mRNA expression in the brain and ACTH release following maternal separation. AT(1) receptor blockade appears to enhance central effects of maternal separation in the neonate, suggesting a suppressing function of brain RAS during the SHRP. Taken together, our results illustrate the molecular adaptations that occur in the paraventricular nucleus following maternal separation and identify signaling cascades, that control stress system activity in the neonate. Keywords: phenotype
2009-07-22 | GSE14687 | GEO
Project description:Hypertension and persistent activation of the renin-angiotensin system (RAS) are predisposing factors for development of acute kidney injury (AKI). Although bone marrow-derived stromal cells (BMSCs) have shown therapeutic promise in treatment of AKI, the impact of pathological RAS on BMSC functionality has remained unresolved. RAS and its local components in the bone marrow are involved in several key steps of cell maturation processes. This may also render BMSC population vulnerable to alterations even in the early phases of RAS pathology. We isolated TG-BMSCs from young, end organ disease-free rats with increased RAS activation (human angiotensinogen/renin double transgenic rats; dTGR) that eventually develop hypertension and die of end-organ damage and kidney failure at 8-weeks-of-age. Control cells were isolated from wild-type Sprague-Dawley rats (SD-BMSCs). Cell phenotype, mitochondrial reactive oxygen species (ROS) production and respiration were assessed, and gene expression profiling was carried out using microarrays. Cells’ therapeutic efficacy was evaluated in a rat model of acute ischemia-reperfusion-induced AKI. Serum urea and creatinine were measured at 24h and 48h. Acute tubular damage was scored and immunohistochemistry was used for evaluation for markers of inflammation (MCP-1, ED-1), and kidney injury (KIM-1, NGAL). TG-BMSCs showed distinct mitochondrial morphology, decreased cell respiration, and increased production of ROS. Gene expression profiling revealed a pronounced pro-inflammatory phenotype. In contrast to the therapeutic effect of SD-BMSCs, administration of TG-BMSCs in the AKI model resulted in exacerbation of kidney injury and high mortality. Our results demonstrate that early persistent RAS activation can dramatically compromise therapeutic potential of BMSCs by shift into a pro-inflammatory phenotype with mitochondrial dysfunction. A comparison of transcriptome of a bone marrow-derived stromal cells from a double-transgene rats compared to those from control rats
2014-03-31 | E-GEOD-51593 | biostudies-arrayexpress
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2015-12-12 | E-GEOD-75940 | biostudies-arrayexpress
Project description:Non-enzymatic activation of renin via its interaction with prorenin receptor (PRR) has been proposed as a key mechanism of local renin-angiotensin system (RAS) activation. The presence of renin and angiotensinogen has been reported in the rostral ventrolateral nucleus (RVLM). Overactivation of bulbospinal neurons RVLM is linked to hypertension (HTN). Previous studies have shown that the brain RAS plays a role in the pathogenesis of the deoxycorticosterone (DOCA)-salt HTN model. Thus, we hypothesized that PRR in the RVLM is involved in the local activation of the RAS, facilitating the development of DOCA-salt HTN. Selective PRR ablation targeting the RVLM (PRRRVLM-Null mice) resulted in an unexpected sex-dependent and biphasic phenotype in DOCA-salt HTN. That is, PRRRVLM-Null females (but not males) exhibited a significant delay in achieving maximal pressor responses during the initial stage of DOCA-salt HTN. Female PRRRVLM-Null subsequently showed exacerbated DOCA-salt-induced pressor responses during the “maintenance” phase with a maximal peak at 13 days on DOCA-salt. This exacerbated response was associated with an increased sympathetic drive to the resistance arterioles and the kidney, exacerbated fluid and sodium intake and output in response to DOCA-salt, and induced mobilization of fluids from the intracellular to extracellular space concomitant with elevated vasopressin. Ablation of PRR suppressed genes involved in RAS activation and catecholamine synthesis in the RVLM but also induced expression of genes involved in inflammatory responses. This study illustrates complex and sex-dependent roles of PRR in the neural control of BP and hydromineral balance through autonomic and neuroendocrine systems.
2023-09-14 | GSE235234 | GEO
Project description:Background: The importance of the brain renin-angiotensin system (RAS) incardiovascular function is well accepted. However, not knowing the precise source ofrenin in the brain has been a limitation towards a complete understanding of how the brainRAS operates. Methods: Highly sensitive in situ hybridization techniques and conditionalknockout mice were used to address the location and function of renin in the brainstem.Results: We identified novel renin-expressing cholinergic neurons in the nucleusambiguus (NuAm), a major vagal cardioinhibitory center in the brainstem. The expressionof RAS genes was relatively abundant in the NuAm, implying that angiotensin II mightmediate an important regulatory role in this nucleus and other regions with neuralconnectivity to the NuAm. Then, we generated conditional knockout mice lacking theclassical renin isoform (Ren-aChAT-KO), specifically in cholinergic neurons. Ablation of Ren-a in cholinergic neurons abrogated renin expression in the NuAm. Moreover, studiesusing radiotelemetry, heart rate variability analyses, and pharmacological approachesrevealed that the parasympathetic nervous system is depressed in Ren-aChAT-KO maleswhile augmented in the Ren-aChAT-KO females. Subsequently, transcriptomic approacheswere used to infer putative genes and signaling pathways regulated by renin within theNuAm. Conclusions: This study revealed that renin in cholinergic neurons plays afundamental role in preserving autonomic balance and cardiovascular homeostasis in asex-dependent manner. These findings define the NuAm as an endogenous, local sourceof renin with biological function and serve as conclusive evidence for the presence andfunctionality of the brain RAS.
2024-12-01 | GSE281444 | GEO
Project description:Long non-coding RNAs (LncRNAs) in hypertensives and their mechanisms in regulating blood pressure still remain unexplored. The aim of present study is to construct the profiles of LncRNAs in blood of patients with essential hypertension and healthy controls. Methods and results, LncRNA microarray identified up-regulated, anddown-regulated LncRNAs, in hypertensives compared to their healthy controls. Among them, one vascular smooth muscle (VSM)-specific LncRNA AK096656 (LncVSM) was quantitated in plasma of patients with hypertension and their healthy controls using the real-time qRT-PCR. LncVSM shows specific expression in human arterial vascular smooth muscle cells (HASMCs) and promote its proliferation and migration. Expression profiles and Ingenuity Pathway Analysis (IPA) revealed that LncVSM activated Renin-Angiotensin Signaling (RAS). the overexpression of LncVSM would result hypertension related complications.
2015-12-12 | GSE75940 | GEO
Project description:Hypertension and persistent activation of the renin-angiotensin system (RAS) are predisposing factors for development of acute kidney injury (AKI). Although bone marrow-derived stromal cells (BMSCs) have shown therapeutic promise in treatment of AKI, the impact of pathological RAS on BMSC functionality has remained unresolved. RAS and its local components in the bone marrow are involved in several key steps of cell maturation processes. This may also render BMSC population vulnerable to alterations even in the early phases of RAS pathology. We isolated TG-BMSCs from young, end organ disease-free rats with increased RAS activation (human angiotensinogen/renin double transgenic rats; dTGR) that eventually develop hypertension and die of end-organ damage and kidney failure at 8-weeks-of-age. Control cells were isolated from wild-type Sprague-Dawley rats (SD-BMSCs). Cell phenotype, mitochondrial reactive oxygen species (ROS) production and respiration were assessed, and gene expression profiling was carried out using microarrays. Cells’ therapeutic efficacy was evaluated in a rat model of acute ischemia-reperfusion-induced AKI. Serum urea and creatinine were measured at 24h and 48h. Acute tubular damage was scored and immunohistochemistry was used for evaluation for markers of inflammation (MCP-1, ED-1), and kidney injury (KIM-1, NGAL). TG-BMSCs showed distinct mitochondrial morphology, decreased cell respiration, and increased production of ROS. Gene expression profiling revealed a pronounced pro-inflammatory phenotype. In contrast to the therapeutic effect of SD-BMSCs, administration of TG-BMSCs in the AKI model resulted in exacerbation of kidney injury and high mortality. Our results demonstrate that early persistent RAS activation can dramatically compromise therapeutic potential of BMSCs by shift into a pro-inflammatory phenotype with mitochondrial dysfunction.
2014-03-31 | GSE51593 | GEO
Project description:The AT2-receptor (AT2R) and the receptor MAS are GPCRs within the renin-angiotensin-system mediating protective actions. Their unconventional signaling mechanisms are still not well characterized, but those known display a high degree of similarity. The proposed project is part of a large-scale collaboration with the group of Robson Santos, a leader in Ang1-7/MAS research, aiming at a better characterization of AT2R-MAS signaling and crosstalk. Building up on our finding that the AT2R and MAS heterodimerise and on the mapping of the entire Ang-(1−7)/MAS signaling network by the Santos group, the proposed studies will look at AT2R-MAS signaling in two ways: mapping the AT2R signaling network by quantitative phosphoproteomics and compare it with the MAS network.
2022-11-18 | PXD005802 | Pride