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IGF1 敲低通过 ROS 依赖性 FOXO 激活引起的能量代谢功能障碍阻碍鸡心脏的心肌发育。

IGF1 Knockdown Hinders Myocardial Development through Energy Metabolism Dysfunction Caused by ROS-Dependent FOXO Activation in the Chicken Heart.

机构信息

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.

College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China.

出版信息

Oxid Med Cell Longev. 2019 Dec 24;2019:7838754. doi: 10.1155/2019/7838754. eCollection 2019.

DOI:10.1155/2019/7838754
PMID:31949883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6948330/
Abstract

Insulin-like growth factor 1 (IGF1) is a multifunctional cellular regulatory factor that can regulate cell growth and development by mediating growth hormone stimulation. However, the mechanism of IGF1 dysfunction in cardiomyocyte development is seldom reported. To study this, we employed the models of IGF1 knockdown in chicken embryo in vivo and in cardiomyocytes in vitro. We detected the antioxidant capacity, PI3K/Akt pathway, energy metabolism-related genes, and myocardial development-related genes. Our results revealed that the low expression of IGF1 can significantly suppress the antioxidant capacity and increase the ROS ( < 0.05) levels, activating the AMPK and PI3K pathway by inhibiting the expression of IRS1. We also found that myocardial energy metabolism is blocked through IGF1, GLUT, and IGFBP inhibition, further inducing myocardial developmental disorder by inhibiting Mesp1, GATA, Nkx2.5, and MyoD expression. Altogether, we conclude that low IGF1 expression can hinder myocardial development through the dysfunction of energy metabolism caused by ROS-dependent FOXO activation.

摘要

胰岛素样生长因子 1(IGF1)是一种多功能的细胞调节因子,通过介导生长激素刺激来调节细胞的生长和发育。然而,IGF1 在心细胞发育中功能障碍的机制很少有报道。为了研究这一点,我们在体内鸡胚和体外心肌细胞中采用 IGF1 敲低模型。我们检测了抗氧化能力、PI3K/Akt 通路、能量代谢相关基因和心肌发育相关基因。我们的结果表明,IGF1 的低表达可显著抑制抗氧化能力并增加 ROS(<0.05)水平,通过抑制 IRS1 的表达来激活 AMPK 和 PI3K 通路。我们还发现,通过抑制 IGF1、GLUT 和 IGFBP 的表达,心肌能量代谢被阻断,进一步通过抑制 Mesp1、GATA、Nkx2.5 和 MyoD 的表达,诱导心肌发育障碍。总之,我们得出结论,低 IGF1 表达可通过 ROS 依赖性 FOXO 激活引起的能量代谢功能障碍阻碍心肌发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb1/6948330/9db64550acf6/OMCL2019-7838754.008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb1/6948330/9db64550acf6/OMCL2019-7838754.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb1/6948330/6b7b517486ed/OMCL2019-7838754.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb1/6948330/0f848750b060/OMCL2019-7838754.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb1/6948330/b7273b0e3d18/OMCL2019-7838754.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fb1/6948330/9db64550acf6/OMCL2019-7838754.008.jpg

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