Dataset Information

Identification of Hub Genes in Protective Effect of Astragaloside IV on Aconitine-Induced Cardiac Damage in Zebrafish Based on Bioinformatics Analysis.

ABSTRACT: Accumulating evidence suggests that Astragaloside IV (AS-IV) improves cardiac function and protects the cardiovascular system. However, the molecular targets involved remain ambiguous. In this work, we report research suggesting that AS-IV can antagonize arrhythmias and reduce the cardiac damage induced by aconitine in zebrafish. Zebrafish have certain benefits with respect to studying the effect of drugs on cardiovascular disease. The possible mechanisms involved are analyzed, and hub gene targets are predicted. First, a model of cardiac damage induced by aconitine was created, and then a safe drug concentration of AS-IV was screened, and the appropriate drug dose gradient was selected within a safe drug concentration range. Second, we confirmed the protective effect of AS-IV in the cardiovascular system by observing changes in zebrafish heart rates and the cardiac and vascular structure. Third, we aimed to demonstrate the antagonistic mechanism of AS-IV on heart rate and cardiac damage induced by aconitine in zebrafish, with differentially expressed genes (DEGs) detected by RNA sequencing. The DEGs were then further analyzed by bioinformatic techniques, such as function enrichment analysis, protein-protein interaction network, and DNA-microRNA networks, for example. Next, we predicted the hub genes of the cardiac protective effects of AS-IV. Finally, we validated these genes in different transcriptome sequence datasets of cardiac damage. Thus, we conclude that miR-26b-5p/ATF3/JUN are key targets of AS-IV and play an important role in maintaining cardiac homeostasis and regulating cardiac remodeling.

SUBMITTER: Wang M

PROVIDER: S-EPMC7327619 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Identification of Hub Genes in Protective Effect of Astragaloside IV on Aconitine-Induced Cardiac Damage in Zebrafish Based on Bioinformatics Analysis.

Wang Mingzhu M Shi Yanan Y Yao Lei L Li Qiang Q Wang Youhua Y Li Jianhua J Fu Deyu D

Frontiers in pharmacology 20200624

Accumulating evidence suggests that Astragaloside IV (AS-IV) improves cardiac function and protects the cardiovascular system. However, the molecular targets involved remain ambiguous. In this work, we report research suggesting that AS-IV can antagonize arrhythmias and reduce the cardiac damage induced by aconitine in zebrafish. Zebrafish have certain benefits with respect to studying the effect of drugs on cardiovascular disease. The possible mechanisms involved are analyzed, and hub gene targ ...[more]

PMID: 32670070

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Project description:In this study, we investigated the protective effect of Astragaloside IV (Ast) on mouse podocytes and its possible mechanism of action by constructing a cadmium-induced mouse renal podocytes model. We investigated the effects of cadmium (Cd) toxicity on cell number, morphology, the mitochondrial status of subcellular organelles, protein and gene levels, and the protective effects of Ast by constructing a model of Cd-induced damage to mouse renal podocytes (MPC5) and giving Ast protection at the same time. The results showed that exposure of MPC5 cells to CdCl2 culture medium containing 6.25 μM concentration acted with low cell mortality, but the mortality of MPC5 cells increased with the prolongation of cadmium exposure time. Given Ast, the death rate in the low dose group (12.5 μM) was significantly reduced, while the death rate in the medium dose group (25 μM) was extremely significantly reduced. In comparison to the control group, the Cd-exposed group exhibited a significant increase of 166.7% in malondialdehyde (MDA) content and a significant decrease of 17.1% in SOD activity. The mitochondrial membrane potential was also reduced to varying degrees. However, in the Ast-protected group compared to the Cd-exposed group, the MDA content significantly decreased by 20.8%, the SOD activity decreased by 7.14%, and the mitochondrial membrane potential showed a significant increase. Fluorescence staining of mitochondrial membrane potential indicated that Cd exposure caused mitochondrial apoptosis. In the 12-h cadmium-exposed group, the protein expression of Nephrin in mice significantly decreased by 33.4%. However, the expression of the Desmin protein significantly increased by 67.8%, and the expression of the autophagy protein LC3-II significantly increased by 55.5%. Meanwhile, the expression of PINK1, a mitochondrial autophagy pathway protein, was significantly increased in the 12 h and 24 h cadmium exposure groups. The mRNA level of PINK1 was significantly increased, and that of Parkin was decreased in the 48 h cadmium exposure group. Compared to the Cd-exposed group, the Ast group showed more significant improvements in the expression of podocyte structure, functional proteins, and mitochondrial autophagy pathway proteins. The immunological assay of mitochondrial autophagic pathway proteins further indicated that Cd-induced damage to MPC5 cells might be associated with the dysregulation of mitochondrial autophagy.

Project description:BackgroundOsteoarthritis (OA) is the most common type of arthritis. OA can cause joint pain, stiffness, and loss of function. The pathogenesis of OA is not completely clear. Moreover, there is no effective treatment, and clinical management is limited to symptomatic relief or joint surgery. This study utilized bioinformatics to analyze normal and OA articular cartilage samples to find biomarkers and therapeutic targets for OA.MethodsThe GSE169077 gene chip dataset was downloaded from the public gene chip data platform of the National Biotechnology Information Center. The dataset included 6 samples of OA tissues and 5 samples of healthy cartilage tissues. Differentially expressed genes (DEGs) were screened using the R language "limma" function package under the threshold of log2[fold change (FC)] ≥2 and a P value <0.05. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathways of the target genes were enriched and analyzed using the database for annotation, visualization, and integrated discovery (DAVID), and a protein-protein interaction (PPI) network was further constructed using the search tool for the retrieval of interacting genes/proteins (STRING) database. The coexpression relationship of the genes in the module was visualized and screened with Cytoscape.ResultsA total of 27 DEGs were identified, including 9 downregulated genes and 18 upregulated genes. GO signal pathway enrichment analysis showed involvement in hypoxic response, fibrous collagen trimer, and extracellular matrix structural components. KEGG analysis demonstrated associations with protein digestion and absorption, extracellular matrix receptor interaction, and the peroxisome proliferator-activated receptor signal pathway, among several other pathways. A PPI network was obtained through STRING analysis, and the results were imported into Cytoscape software. The 27 DEGs were sequenced by the cytoHubba plug-in by various calculation methods, and 5 hub genes (COL1A1, COL1A2, POSTN, BMP1, and MMP13) were finally selected. These genes were analyzed by PPI again and annotated with GO and KEGG in different colors.ConclusionsBioinformatics technology effectively identified differential genes in the knee cartilage tissue of healthy controls and patients with OA, providing opportunities to further explore the mechanism and treatment of OA on a transcriptional level.

Project description:Chronic hypoxia can be observed in the heart under physiological or pathophysiological states, including embryonic development or cyanotic congenital heart disease. The aim of the present study was to examine gene expression profiles of chronically hypoxic myocardium and to explore the pathophysiological mechanisms by which the heart adapts to chronic hypoxia. Raw data from the next‑generation sequencing data set GSE36761 were downloaded from the Gene Expression Omnibus database. The data set comprised 30 specimens, including 8 healthy myocardia and 22 tetralogy of Fallot (TOF) congenital cardiac malformations; only 7 original data sets of healthy myocardia were obtained, and 5/22 TOFs were excluded. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed genes (DEGs) were performed. Furthermore, network analysis of DEGs using Cytoscape software based on protein‑protein interaction (PPI) data was also conducted. A total of 1,260 DEGs were selected, of which 926 DEGs were enriched in 83 GO biological process terms, including extracellular matrix organization, regeneration and monocyte chemotaxis. Furthermore, 406 DEGs were enriched in 13 KEGG pathways, including cytokine‑cytokine receptor interaction, focal adhesion and apoptosis. PPI network analysis indicated that six hub genes with correlated degree scores >25 among nodes were identified, including G protein subunit β4, C‑C motif chemokine receptor (CCR)1, CCR2, platelet factor 4, catenin β1 and Jun proto‑oncogene (JUN). Of these, JUN was enriched in GO terms of regeneration and neuron projection regeneration, and in KEGG pathways of focal adhesion, apoptosis and Chagas disease (American trypanosomiasis). The present bioinformatics analysis of these DEGs and hub genes may provide a molecular insight to the role of diverse genes in the pathophysiology of chronically hypoxic myocardium and in myocardial adaptation to chronic hypoxia.

Dataset Information

Identification of Hub Genes in Protective Effect of Astragaloside IV on Aconitine-Induced Cardiac Damage in Zebrafish Based on Bioinformatics Analysis.

Publications

Identification of Hub Genes in Protective Effect of Astragaloside IV on Aconitine-Induced Cardiac Damage in Zebrafish Based on Bioinformatics Analysis.

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