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Molecular mechanisms of cannabinoid type II receptor agonists in a mouse model of psychological stress-induced cardiac injury revealed by whole transcriptomic analysis

ABSTRACT: To investigate the mechanisms of chronic psychological stress-induced cardiac injury and the protective mechanisms of cannabinoid type II agonists in a model of psychological stress-induced cardiac injury We constructed a mouse chronic psychological stress model based on a chronic unpredictable stress pattern. Mice were randomly divided into control, case (psychological stress group), and treatment groups (post-stress with the cannabinoid type II receptor agonist JWH133) to begin a 3-week psychological stress procedure, and cardiac tissue was subsequently removed for whole-transcriptome sequencing

ORGANISM(S): Mus musculus

PROVIDER: GSE210820 | GEO | 2022/12/30

REPOSITORIES: GEO

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Project description:Type 2 diabetes mellitus (T2DM) is a complex metabolic disease with multiple etiologies, involving both genetic and environmental factors. With changes associated with modern life, increasing attention has been paid to chronic psychological stressors such as work stress. Chronic psychological stress can induce or aggravate diabetes mellitus, and conversely, with the deterioration of T2DM, patients often experience different degrees of depression, anxiety, and other negative emotions. To elucidate the role of ZiBuPiYin recipe (ZBPYR) in regulating the liver mitochondria-associated endoplasmic reticulum membrane proteome to improve T2DM with chronic psychological stress, differentially expressed proteins (DEPs) were identified among Zucker lean littermates (control group), chronic psychological stress T2DM rats (model group), and ZBPYR administration rats (ZBPYR group) via iTRAQ with LC-MS/MS. Using Mfuzz soft clustering analysis, DEPs were divided into six different clusters. Clusters 1-6 contained 5, 68, 44, 57, 28, and 32 DEPs, respectively. Given that ZBPYR can alleviate T2DM symptoms and affect exploratory behavior during T2DM with chronic psychological stress, we focused on the clusters with opposite expression trends between model:control and ZBPYR:model groups. We screened out the DEPs in clusters 1, 3, and 4, which may be good candidates for the prevention and treatment of T2DM with chronic psychological stress, and further conducted bioinformatics analyses. DEPs were mainly involved in the insulin signaling pathway, oxidative phosphorylation, tricarboxylic acid cycle, amino acid metabolism, lysosome-related processes, and lipid metabolism. This may indicate the pathogenic basis of T2DM with chronic psychological stress and the potential therapeutic mechanism of ZBPYR. In addition, two key proteins, a lysosome-associated protein (Lamp2) and tricarboxylic acid cycle-related protein (Suclg1), may represent novel biomarkers for T2DM with chronic psychological stress and drug targets of ZBPYR.

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Molecular mechanisms of cannabinoid type II receptor agonists in a mouse model of psychological stress-induced cardiac injury revealed by whole transcriptomic analysis

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