胰岛素样生长因子-1/胰岛素样生长因子-1受体信号通路调控肝纤维化的作用机制

崔艳; 李京涛; 焦俊喆; 常占杰; 张海博

doi:10.12449/JCH260227

胰岛素样生长因子-1/胰岛素样生长因子-1受体信号通路调控肝纤维化的作用机制

DOI: 10.12449/JCH260227

1.
陕西中医药大学第一临床医学院，陕西咸阳 712000
2.
陕西中医药大学附属医院肝病一科，陕西咸阳 712000

基金项目:

国家自然科学基金 (82174330);

国家自然科学基金 (82374418);

陕西省科技厅科研基金 (2024JC-YBMS-650);

陕西省科技厅科研基金 (2024SF-YBXM-528);

陕西省科技厅创新团队 (2022TD-55);

陕西省中医药管理局 (SZY-KJCYC-2023-049);

陕西省中医药管理局 (SZY-KJCYC-2023-087);

中医药防治肝病“炎-癌”转变研究创新团队 (2019-YL05)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：崔艳负责课题设计，资料分析，撰写论文；焦俊喆、常占杰参与收集数据，修改论文；李京涛、张海博负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
张海博， 15289317954@163.com （ORCID： 0000-0003-1755-1813）

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- 被引次数: 0
出版历程
- 收稿日期: 2025-06-09
- 录用日期: 2025-07-16
- 出版日期: 2026-02-25

The mechanism of action of the insulin-like growth factor-1/insulin-like growth factor-1 receptor signaling pathway in regulating liver fibrosis

1.
The First Clinical Medical College，Shaanxi University of Chinese Medicine，Xianyang，Shaanxi 712000，China
2.
First Department of Hepatology，The Affiliated Hospital of Shaanxi University of Chinese Medicine，Xianyang，Shaanxi 712000，China

Research funding:

National Natural Science Foundation of China (82174330);

National Natural Science Foundation of China (82374418);

Shaanxi Province Science and Technology Department Research Fund (2024JC-YBMS-650);

Shaanxi Province Science and Technology Department Research Fund (2024SF-YBXM-528);

Shaanxi Province Science and Technology Department Innovation Team (2022TD-55);

Shaanxi Province Traditional Chinese Medicine Administration (SZY-KJCYC-2023-049);

Shaanxi Province Traditional Chinese Medicine Administration (SZY-KJCYC-2023-087);

Research and Innovation Team for Prevention and Treatment of Liver Disease “Inflammation‑Cancer” Transformation with Traditional Chinese Medicine (2019-YL05)

More Information

Corresponding author: ZHANG Haibo， 15289317954@163.com （ORCID： 0000-0003-1755-1813）

摘要

摘要: 肝纤维化由病毒感染、酒精摄入和代谢相关损伤等多种因素引起，导致正常组织被纤维瘢痕替代。胰岛素样生长因子1（IGF-1）作为一种细胞增殖调控因子，通过与其受体（IGF-1R）结合，参与调控细胞周期、促进细胞增殖与分化，并抑制细胞凋亡。研究表明，IGF-1/IGF-1R信号通路可通过影响肝细胞的衰老和凋亡、肝星状细胞的活化与增殖以及内皮细胞的功能失调等调控肝纤维化进程。此外，IGF-1/IGF-1R信号系统还可调控DNA损伤修复、细胞增殖、脂质代谢、细胞衰老及氧化应激等多种机制，为肝纤维化的预防和治疗提供了新的策略与潜在靶点。本文总结了IGF-1/IGF-1R及其信号转导系统在不同细胞中通过调控DNA损伤修复介导肝纤维化的作用机制，以期为肝纤维化的治疗提供理论依据。
- 胰岛素样生长因子Ⅰ /
- 肝纤维化 /
- DNA损伤 /
- 信号传导
Abstract: Liver fibrosis is caused by various factors such as viral infection， alcohol intake， and metabolism-related damage， leading to the replacement of normal tissue by fibrous scars. As a regulatory factor for cell proliferation， insulin-like growth factor 1 （IGF-1） participates in the regulation of cell cycle， the promotion of cell proliferation and differentiation， and the inhibition of cell apoptosis by binding to its receptor insulin-like growth factor-1 receptor （IGF-1R）. Studies have shown that the IGF-1/IGF-1R signaling pathway can regulate the process of liver fibrosis by affecting the senescence and apoptosis of hepatocytes， the activation and proliferation of hepatic stellate cells， and the dysfunction of endothelial cells. In addition， the IGF-1/IGF-1R signaling system can also regulate multiple mechanisms such as DNA damage repair， cell proliferation， lipid metabolism， cell senescence， and oxidative stress， thereby providing new strategies and potential targets for the prevention and treatment of liver fibrosis. This article summarizes the mechanism of action of IGF-1/IGF-1R and its signal transduction system in mediating liver fibrosis by regulating DNA damage repair in different cells， in order to provide a theoretical basis for the treatment of liver fibrosis.
- Insulin-Like Growth Factor I /
- Hepatic Fibrosis /
- DNA Damage /
- Signal Transduction

HTML全文

注： IGF-1，胰岛素样生长因子1；IGF-1R，胰岛素样生长因子1受体；HR，同源重组；NHEJ，非同源末端连接；PPAR，过氧化物酶体增殖物激活受体；HSC，肝星状细胞；ROS，活性氧；miRNA，微RNA；p53，肿瘤蛋白p53。

图 1 IGF-1/IGF-1R信号通路调控肝纤维化的作用机制

Figure 1. The regulatory mechanism of IGF-1/IGF-1R signaling pathway in hepatic fibrosis

下载: 全尺寸图片幻灯片

注： IGF-1，胰岛素样生长因子1；IGF-1R，胰岛素样生长因子1受体；lncRNA-p21，长链非编码RNAp21； PI3K，磷脂酰肌醇3激酶；AKT，蛋白激酶B；MAPK，丝裂原激活的蛋白激酶；ERK，胞外信号调节激酶；PCNA，增殖细胞核抗原；RRM2，核糖核苷酸还原酶M2 亚基； dNTP，脱氧核糖核苷三磷酸； EGFR，表皮生长因子受体。

图 2 IGF-1/IGF-1R轴在肝细胞中介导肝纤维化的机制

Figure 2. The mechanism by which the IGF-1/IGF-1R axis mediates hepatic fibrosis in hepatocytes

下载: 全尺寸图片幻灯片

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