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Gastrodin alleviates cardiac hypertrophy by inhibition of insulin-like growth factor type 2/insulin-like growth factor type 2 receptor

ABSTRACT: Gastrodin alleviates cardiac hypertrophy by inhibition of insulin-like growth factor type 2/insulin-like growth factor type 2 receptor

PROVIDER: PRJNA689477 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13347840_1.fastq.gz	Fastqsanger.gz
	SRR13347840_2.fastq.gz	Fastqsanger.gz
	SRR13347841_1.fastq.gz	Fastqsanger.gz
	SRR13347841_2.fastq.gz	Fastqsanger.gz
	SRR13347842_1.fastq.gz	Fastqsanger.gz

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Project description:Pathological cardiac hypertrophy is commonly associated with an upregulation of fetal genes, fibrosis, cardiac dysfunction, and heart failure. Previous studies have demonstrated that gastrodin (GAS) exerts cardioprotective action in the treatment of cardiac hypertrophy. However, the mechanism by which GAS protects against cardiac hypertrophy is yet to be elucidated. A mouse model of myocardial hypertrophy was established using an angiotensin II (Ang II) induction. GAS (5 or 50 mg/kg/d) was orally administered every day starting 7 days prior to the Ang II infusion combined with sham-operated controls. Heart samples from each group were collected for RNA sequencing. Using bioinformatics analysis, the key differentially expressed genes (DEGs) that are involved in reversing cardiac function were identified. Through bioinformatics analysis, the key DEGs that are involved in GAS's inhibition of Ang II-induced abnormal gene expression within the heart were identified. This was further validated using quantitative real-time PCR and Western blotting in neonatal rat cardiomyocytes (NRCMs). Oral administration of GAS significantly suppressed the Ang II-induced increase in heart size and heart weight to body weight. Furthermore, pretreatment of the NRCMs with GAS led to a dose-dependent inhibition of Ang II-induced increases in Nppb mRNA expression. We identified 620 upregulated and 87 downregulated Ang II-induced DEGs II, among which the expression patterns of 58 and 146 genes were inverted by low-dose and high-dose GAS, respectively. These inverted DEGs were found to be mainly enriched in the biological processes of regulation of Ras protein signal transduction, heart contraction, covalent chromatin modification, glucose metabolism, and positive regulation of cell cycle. Among them, the insulin-like growth factor type 2 (Igf2) gene, which was found to be highly reversed and downregulated by GAS, served as a core gene linking energy metabolism, immune regulation, and systemic development. Subsequent functional verification demonstrated that IGF2, and its receptor IGF2R, is one of the targets of GAS that helps protect against cardiac hypertrophy. Taken together, we have identified, for the first time, IGF2/IGF2R as a potential target influenced by GAS in the prevention of cardiac hypertrophy.

Project description:Gastrodia elata Blume (Orchidaceae) is an important Chinese medicine with several functional components. In the life cycle of G. elata, the orchid develops a symbiotic relationship with two compatible mycorrhizal fungi Mycena spp. and Armillaria mellea during seed germination to form vegetative propagation corm and vegetative growth to develop tubers, respectively. Gastrodin (p-hydroxymethylphenol-beta-D-glucoside) is the most important functional component in G. elata, and gastrodin significantly increases from vegetative propagation corms to tubers. To address the gene regulation mechanism in gastrodin biosynthesis in G. elata, a comparative analysis of de novo transcriptome sequencing among the vegetative propagation corms and tubers of G. elata and A. mellea was conducted using deep sequencing. Transcriptome comparison between the vegetative propagation corms and juvenile tubers of G. elata revealed 582 differentially expressed unigenes, of which 415 and 167 genes were, respectively up-regulated (fold-change â?¥ 2, p-value < 0.05) and down-regulated (fold-change â?¤ 0.5, p-value <0.05) in juvenile tubers. After Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, forty-seven up-regulated unigenes with enzyme commission (EC) were assigned to 269 isogroups involved in 100 different pathways, and twenty-four down-regulated unigenes with enzyme commission (EC) were assigned to 586 isogroups, involved in 167 different pathways. The analysis of the isogroup genes from all pathways revealed that the two unigenes at locus 25,051 (one of monooxygenases) and locus 22,288 (one of glycosyltransferases) might participate in hydroxylation and glucosylation in the gastrodin biosynthetic pathway. The gene expression of the two unique unigenes encoding monooxygenase and glycosyltransferase significantly increases from vegetative propagation corms to tubers, and the molecular basis of gastrodin biosynthesis in the tubers of G. elata is proposed. Transcriptome comparative between vegetative propagation corms and tubers of G. elata, and between tubers of G. elata (symbiosis A. mellea) and A. mellea

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Gastrodin alleviates cardiac hypertrophy by inhibition of insulin-like growth factor type 2/insulin-like growth factor type 2 receptor

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