Comparison of transcriptome landscape between adenine-induced and nephrectomy-induced uremic cardiomyopathy
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ABSTRACT:
PROVIDER: PRJNA1136533 | ENA |
REPOSITORIES: ENA
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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.
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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.
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