IGF1 敲低通过鸡心脏中 ROS 依赖性 FOXO 激活引起的能量代谢功能障碍阻碍心肌发育

IGF1 Knockdown Hinders Myocardial Development through Energy Metabolism

Dysfunction Caused by ROS-Dependent FOXO Activation in the Chicken Heart

Keywords：Insulin; Cardiomyocytes; Energy Metabolism
关键词：胰岛素；心肌细胞；能量代谢

非哺乳动物：鸟类
作者：Gong Y, Yang J, Liu Q, Cai J, Zheng Y, Zhang Y, Yu D, Liu H, Zhang Z
出版期刊：《Oxidative Medicine and Cellular Longevity》 2019/12/24

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 (P＜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.

文章摘要：

胰岛素样生长因子 1 (IGF1) 是一种多功能细胞调节因子，可通过介导生长激素刺激来调节细胞生长发育。然而，IGF1功能障碍在心肌细胞发育中的作用机制鲜有报道。为了研究这一点，我们采用了体内鸡胚和体外心肌细胞中的 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。我们的研究结果表明，IGF1 的低表达可以显着抑制抗氧化能力并增加 ROS (P＜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 来阻断心肌能量代谢，通过抑制 Mesp1、GATA、Nkx2.5 和 MyoD 表达进一步诱导心肌发育障碍。总之，我们得出结论，低 IGF1 表达可以通过 ROS 依赖性 FOXO 激活引起的能量代谢功能障碍阻碍心肌发育。

点击链接即可查看和下载文章：https://www.hindawi.com/journals/omcl/2019/7838754/
文章题目、关键词与摘要译文仅用于参考。