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Gastrodin Exerts Cardioprotective Action via Inhibition of Insulin-Like Growth Factor Type 2/Insulin-Like Growth Factor Type 2 Receptor Expression in Cardiac Hypertrophy
[Image: see text] 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, th...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264851/ https://www.ncbi.nlm.nih.gov/pubmed/34250336 http://dx.doi.org/10.1021/acsomega.1c00797 |
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author | Lu, Jun Ma, Xin Gao, Wen-Cong Zhang, Xin Fu, Yuanling Liu, Qian Tian, Lixiang Qin, Xiao-Dan Yang, Weimin Zheng, Hong-Yi Zheng, Chang-Bo |
author_facet | Lu, Jun Ma, Xin Gao, Wen-Cong Zhang, Xin Fu, Yuanling Liu, Qian Tian, Lixiang Qin, Xiao-Dan Yang, Weimin Zheng, Hong-Yi Zheng, Chang-Bo |
author_sort | Lu, Jun |
collection | PubMed |
description | [Image: see text] 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. |
format | Online Article Text |
id | pubmed-8264851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-82648512021-07-09 Gastrodin Exerts Cardioprotective Action via Inhibition of Insulin-Like Growth Factor Type 2/Insulin-Like Growth Factor Type 2 Receptor Expression in Cardiac Hypertrophy Lu, Jun Ma, Xin Gao, Wen-Cong Zhang, Xin Fu, Yuanling Liu, Qian Tian, Lixiang Qin, Xiao-Dan Yang, Weimin Zheng, Hong-Yi Zheng, Chang-Bo ACS Omega [Image: see text] 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. American Chemical Society 2021-06-21 /pmc/articles/PMC8264851/ /pubmed/34250336 http://dx.doi.org/10.1021/acsomega.1c00797 Text en © 2021 The Authors. Published by American Chemical Society Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Lu, Jun Ma, Xin Gao, Wen-Cong Zhang, Xin Fu, Yuanling Liu, Qian Tian, Lixiang Qin, Xiao-Dan Yang, Weimin Zheng, Hong-Yi Zheng, Chang-Bo Gastrodin Exerts Cardioprotective Action via Inhibition of Insulin-Like Growth Factor Type 2/Insulin-Like Growth Factor Type 2 Receptor Expression in Cardiac Hypertrophy |
title | Gastrodin Exerts Cardioprotective Action via Inhibition
of Insulin-Like Growth Factor Type 2/Insulin-Like Growth Factor Type
2 Receptor Expression in Cardiac Hypertrophy |
title_full | Gastrodin Exerts Cardioprotective Action via Inhibition
of Insulin-Like Growth Factor Type 2/Insulin-Like Growth Factor Type
2 Receptor Expression in Cardiac Hypertrophy |
title_fullStr | Gastrodin Exerts Cardioprotective Action via Inhibition
of Insulin-Like Growth Factor Type 2/Insulin-Like Growth Factor Type
2 Receptor Expression in Cardiac Hypertrophy |
title_full_unstemmed | Gastrodin Exerts Cardioprotective Action via Inhibition
of Insulin-Like Growth Factor Type 2/Insulin-Like Growth Factor Type
2 Receptor Expression in Cardiac Hypertrophy |
title_short | Gastrodin Exerts Cardioprotective Action via Inhibition
of Insulin-Like Growth Factor Type 2/Insulin-Like Growth Factor Type
2 Receptor Expression in Cardiac Hypertrophy |
title_sort | gastrodin exerts cardioprotective action via inhibition
of insulin-like growth factor type 2/insulin-like growth factor type
2 receptor expression in cardiac hypertrophy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264851/ https://www.ncbi.nlm.nih.gov/pubmed/34250336 http://dx.doi.org/10.1021/acsomega.1c00797 |
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