Role of adipose tissue Na/K ATPase signaling in uremic cardiomyopathy
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ABSTRACT:
PROVIDER: PRJNA824077 | ENA |
REPOSITORIES: ENA
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Project description:The objective of the present study is to explore the role of human MSC derived adipocytes transduced with/without lenti adipo-NaKtide or lenti adipo-scrambled NaKtide in experimental uremic cardiomyopathy. We investigated the pathophysiological changes in recipient mice that underwent partial nephrectomy surgery, as a model of uremic cardiomyopathy, and implanted with NaKtide transfected human MSC derived adipocytes. We aimed to demonstrate that adipocyte specific NaKtide reprograms the adipocyte phenotype and transplantation of these metabolically healthy adipocytes in diseased condition exhibits improved systemic and cardiovascular function, through intra-organ crosstalk.
2023-04-05 | GSE200328 | GEO
Project description:Adenine and nephrectomy can be used to establish models of uremic cardiomyopathy in rodents. Although these two approaches cause similar phenotypes of heart, adenine may directly act on cardiomyocytes and lead to different molecular changes from nephrectomy-induced uremic cardiomyopathy. Transcriptome analysis on left ventricles showed 789 upregulated and 345 downregulated genes in mice with nephrectomy-induced uremic cardiomyopathy compared to control mice, while 432 upregulated and 155 downregulated genes in mice with adenine diet-induced uremic cardiomyopathy compared to control mice. Functional analysis revealed that these DEGs were involved in pathways related to immune inflammation, metabolic responses, and synaptic transmission. Further analysis demonstrated that nephrectomy-induced uremic cardiomyopathy has enhanced cell cycle process/extracellular matrix remodeling and suppressed fatty acid metabolism, whereas adenine diet-induced uremic cardiomyopathy only exhibits increased inflammatory response/extracellular matrix remodeling. Compared with nephrectomy-induced uremic cardiomyopathy, adenine diet-induced uremic cardiomyopathy showed improved oxidative phosphorylation, aerobic electron transport chain, and tricarboxylic acid cycle, and suppressed cell cycle-related process, indicating that adenine and its derivates may affect the process of chronic kidney induced cardiac changes.
2024-07-23 | GSE272375 | GEO
Project description:Gene expression profiles in experimental uremic cardiomyopathy.
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Project description:Purpose: To define differentially regulated pathways in heart tissue from mice with chornic kidney disease (CKD) compared to age-matched controls. Methods: CKD was induced in 5-week-old, male 129X1/SvJ mice (JAX) through five-sixths nephrectomy in a two-step surgery (n=5). Age-matched mice undergoing bilateral sham surgeries served as controls (n=5). Heart tissue was collected at 8 weeks of CKD for next generation sequencing. Results: Hearts from mice with uremic cardiomyopathy yielded over 1,000 differentially-expressed mRNA transcripts compared to hearts from age-matched, sham-operated mice. Ingenuity biofunctions analysis identified significant enrichment for genes involved in Tissue Morphology, Immune Cell Trafficking, Cardiovascular Development and Function, and Humoral Immune Response. We focused on Ingenuity canonical pathways involving inflammation and immune system function including pathways needed for a T-cell mediated response: leukocyte extravasation, antigen presentation, dendritic cell maturation, T cell co-stimulatory signaling, and T-helper cell differentiation. Conclusions: Left ventricles from mice with CKD display differential expression in a number of pathways suggesting inflammation and surprisingly involved genes involved in the adaptive immune system.
2019-02-12 | GSE106385 | GEO
Project description:Adipocyte-specific expression of Na,K-ATPase signaling antagonist, NaKtide, has been shown to ameliorate the pathophysiological consequences of obesity and improve diseased phenotype. Recent studies have established that the release of adipocytokines and other bioactive mediators in obesity contributes to neurodegeneration. This study utilizes a mechanistic approach and characterizes the hippocampal transcriptome in comparison with transcriptomic changes in liver, visceral and subcutaneous adipose tissue. RNAseq analysis in high fat diet fed transgenic mice showed large scale differential gene expression as well as modulation of several biological pathways in hippocampus, liver, visceral and subcutaneous adipose tissue, which were attenuated by doxycycline induced adipocyte specific NaKtide expression.
2021-11-10 | GSE164293 | GEO
Project description:Exposure to hypoxia requires adaptive mechanisms for survival. During acute hypoxia, Na,K-ATPase endocytosis in alveolar epithelial cells (AEC) occurs via protein kinase C zeta (PKCζ) phosphorylation of α1- Na,K-ATPase independently of the hypoxia inducible factor (HIF). However, exaggerated Na,K-ATPase down-regulation leads to cell death. Here we report that during prolonged hypoxia plasma membrane Na,K-ATPase levels were maintained at ~50% of normoxic values due to HIF mediated regulation of HOIL-1L which targets PKCζ for degradation. Silencing HOIL-1L in the lung epithelium prevented PKCζ degradation causing Na,K-ATPase downregulation. Accordingly, HIF regulation of HOIL-1L targets the phosphorylated PKCζ for degradation and serves as an hypoxia-adaptive mechanism to stabilize the Na,K-ATPase avoiding significant lung injury.
2018-02-14 | GSE102107 | GEO
Project description:Comparison of transcriptome landscape between adenine-induced and nephrectomy-induced uremic cardiomyopathy
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Project description:Adipocyte-specific expression of Na,K-ATPase signaling antagonist, NaKtide, has been shown to ameliorate the pathophysiological consequences of obesity and improve diseased phenotype. Recent studies have established that the release of adipocytokines and other bioactive mediators in obesity contributes to neurodegeneration. This study utilizes a mechanistic approach and characterizes the hippocampal transcriptome in comparison with transcriptomic changes in liver, visceral and subcutaneous adipose tissue. RNAseq analysis in high fat diet fed transgenic mice showed large scale differential gene expression as well as modulation of several biological pathways in hippocampus, liver, visceral and subcutaneous adipose tissue, which were attenuated by doxycycline induced adipocyte specific NaKtide expression.
2021-11-10 | GSE164294 | GEO
Project description:Familial hemiplegic migraine is an episodic neurological disorder characterized by transient sensory and motor symptoms and signs. Mutations of the ion pump alpha2-Na/K ATPase represent a key genetic cause of familial hemiplegic migraine, but the mechanisms by which alpha2-Na/K ATPase mutations lead to the migraine phenotype remain incompletely understood. Here, we unexpectedly find that mice in which alpha2-Na/K ATPase is conditionally deleted in astrocytes display episodic transient motor paralysis. Functional neuroimaging reveals that conditional knockout of alpha2-Na/K ATPase triggers spontaneous cortical spreading depression events that are associated with low voltage activity events upon EEG monitoring, which in turn correlate with transient motor impairment in these mice. Transcriptomic and metabolomic analyses show that loss of alpha2-Na/K ATPase alters metabolic gene expression in astrocytes in vivo with consequent elevation of serine and glycine in the brain. Strikingly, feeding alpha2-Na/K ATPase knockout mice a serine- and glycine-free diet reverses the phenotype of transient motor impairment. Together, our findings define a novel metabolic mechanism regulated by astrocytic alpha2-Na/K ATPase that triggers episodic transient motor paralysis in mice, laying the foundation for potential new treatment strategies for patients with familial hemiplegic migraine.
2020-10-20 | GSE145102 | GEO
Project description:Whole hearts from wild-type and Na,K-ATPase alpha 1 het. mice. Adult male, 8-16 weeks old on a 129/BSwiss background. Keywords: repeat sample
2004-11-19 | GSE1134 | GEO