miR-27b-5p通过靶向IRS2抑制PI3K/AKT信号通路调控鸡肝脏疾病

doi:10.1016/j.jia.2023.04.010

Journal of Integrative Agriculture ›› 2023, Vol. 22 ›› Issue (11): 3500-3516.DOI: 10.1016/j.jia.2023.04.010

miR-27b-5p通过靶向IRS2抑制PI3K/AKT信号通路调控鸡肝脏疾病

收稿日期:2022-12-28 接受日期:2023-03-07 出版日期:2023-11-20 发布日期:2023-11-09

miR-27b-5p regulates chicken liver disease via targeting IRS2 to suppress the PI3K/AKT signal pathway

ZHAO Jing^1*, WU Ya-mei^1*, ZHANG Yao^1#, TANG Shu-yue¹, HAN Shun-shun¹, CUI Can¹, TAN Bo², YU Jie³, KANG Hou-yang⁴, CHEN Guang-deng⁵, MA Meng-gen⁵, ZHU Qing^1#,YIN Hua-dong^1#

¹ Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, P.R.China
² College of Forestry, Sichuan Agricultural University, Chengdu 611130, P.R.China
³ Key Laboratory for Animal Disease Resistance Nutrition of China, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, P.R.China
⁴ Triticeae Research Institute, Sichuan Agricultural University, Chengdu 611130, P.R.China
⁵ College of Resources, Sichuan Agricultural University, Chengdu 611130, P.R.China

Received:2022-12-28 Accepted:2023-03-07 Online:2023-11-20 Published:2023-11-09
About author:ZHAO Jing, E-mail: zhaojing@stu.sicau.edu.cn; WU Ya-mei, E-mail: wuyamei@stu.sicau.edu.cn; ZHANG Yao, E-mail: zhangyao@sicau.edu.cn; #Correspondence YIN Hua-dong, E-mail: yinhuadong@sicau.edu.cn; ZHU Qing, E-mail: zhuqing@sicau.edu.cn * These authors contributed equally to this study.
Supported by:
This experiment was financially supported by the National Key Research and Development Program of China (2021YFD1300600), the Sichuan Science and Technology Program, China (2021YFYZ0007 and 2022YFYZ0005), and the China Agriculture Research System of MOF and MARA (CARS-40-K06).

摘要/Abstract

摘要：

肝脏是鸡最重要的器官之一，具有储存肝糖原、合成蛋白质、解毒和脱氧等生理功能。肝脏的代谢和生长是一个复杂过程，受到环境、饮食和遗传等因素的调控。microRNAs (miRNAs) 作为转录后调控因子可参与多种生理过程。越来越多的证据表明，miR-27b-5p在不同物种的肝脏发育和代谢中发挥着至关重要的调控作用。但是miR-27b-5p在鸡肝脏中的潜在作用尚未被探索。在本次试验中，我们首先发现脂肪肝鸡血清中TG和TC的含量显著高于正常鸡，而VLDL和血清激素(FSH、LH和E2)含量较正常组鸡显著降低。随后的研究发现miR-27b-5p在鸡脂肪肝中表达量较高，表明miR-27b-5p可能参与调节鸡肝脏的发育和代谢。接下来，我们探索了miR-27b-5p在鸡肝脏中的潜在功能，发现miR-27b-5p能促进脂肪合成、增加细胞内氧化应激水平和炎症反应，并最终导致肝细胞发生凋亡。之后，我们又构建了miR-27b-5p与其靶基因间的调控机制，发现miR-27b-5p通过吸附IRS2来调控PI3K/AKT信号通路。此外，我们又探索了IRS2在鸡肝脏细胞中的效应，结果表明干扰IRS2与外源性过表达miR-27b-5p具有相同的作用。最终，我们的研究揭示miR-27b-5p通过结合IRS2来抑制PI3K/AKT信号通路，从而导致鸡肝脏脂肪变性、氧化应激，炎症反应和细胞凋亡。

Abstract:

The liver is a vital organ in chickens that performs a number of crucial physiological functions, including the storage of hepatic glycogen, protein synthesis, detoxification, and deoxidation. The growth and metabolism of the liver are complex processes influenced by factors such as environment, diet, and genetics. MicroRNAs (miRNAs), as post-transcriptional regulatory molecules, play a role in various biological processes. There is growing evidence that miR-27b-5p plays a key role in the regulation of liver development and metabolism in various species. However, its role in chicken livers has yet to be determined. In our experiment, we found that chickens with fatty livers had significantly higher levels of serum triglyceride (TG) and total cholesterol (TC) compared to the normal chickens, while the control group had significantly higher levels of very low-density lipoprotein (VLDL) and serum hormones. Further research showed that the mRNA of miR-27b-5p was highly expressed in fatty livers. By exploring the function of miR-27b-5p in chicken livers, we discovered that it promotes lipogenesis, oxidative stress, and inflammatory responses, leading to hepatocyte apoptosis. Our study also established the mechanism by which miR-27b-5p interacts with its target gene, and found that miR-27b-5p targets insulin receptor substrate 2 (IRS2) and modulates the PI3K/AKT signaling pathway. Additionally, our investigation of IRS2 in chicken hepatocytes revealed that knocking down IRS2 has the same effects as overexpressing miR-27b-5p. In conclusion, our study revealed that miR-27b-5p directly binds to IRS2, inhibiting the PI3K/AKT signaling pathway and causing steatosis, oxidative stress, inflammation, and apoptosis in chicken liver.

Key words: miR-27b-5p , IRS2 , lipogenesis , oxidative stress , inflammation , apoptosis

ZHAO Jing, WU Ya-mei, ZHANG Yao, TANG Shu-yue, HAN Shun-shun, CUI Can, TAN Bo, YU Jie, KANG Hou-yang, CHEN Guang-deng, MA Meng-gen, ZHU Qing, YIN Hua-dong. miR-27b-5p通过靶向IRS2抑制PI3K/AKT信号通路调控鸡肝脏疾病[J]. Journal of Integrative Agriculture, 2023, 22(11): 3500-3516.

ZHAO Jing, WU Ya-mei, ZHANG Yao, TANG Shu-yue, HAN Shun-shun, CUI Can, TAN Bo, YU Jie, KANG Hou-yang, CHEN Guang-deng, MA Meng-gen, ZHU Qing, YIN Hua-dong. miR-27b-5p regulates chicken liver disease via targeting IRS2 to suppress the PI3K/AKT signal pathway[J]. Journal of Integrative Agriculture, 2023, 22(11): 3500-3516.

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miR-27b-5p通过靶向IRS2抑制PI3K/AKT信号通路调控鸡肝脏疾病

miR-27b-5p regulates chicken liver disease via targeting IRS2 to suppress the PI3K/AKT signal pathway

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