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整合素与非酒精性脂肪性肝病相关肝脏疾病:临床关联、病理生理机制及药理学意义

Integrins and NAFLD-associated liver diseases: clinical associations, pathophysiological mechanisms and pharmacological implications.

作者信息

Ni Yangyue, Huang Mengwen, Chen Shiyang, Wang Shihui, Chen Jianfeng

机构信息

Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.

Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2024 Sep 14;56(11):1573-1583. doi: 10.3724/abbs.2024149.


DOI:10.3724/abbs.2024149
PMID:40384047
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11659783/
Abstract

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and poses a substantial health burden with increasing incidence globally. NAFLD encompasses a spectrum extending from hepatic steatosis to nonalcoholic steatohepatitis (NASH), with the possibility of progressing to cirrhosis or, in severe instances, hepatocellular carcinoma (HCC). NAFLD extends beyond simple metabolic disruption and involves multiple immune cell-mediated inflammatory processes. Integrins are a family of heterodimeric transmembrane cell adhesion receptors that regulate various aspects of NAFLD onset and progression, including hepatocellular steatosis, hepatic stellate cell (HSC) activation and immune cell infiltration. In this review, we comprehensively summarize the involvement of integrins in NAFLD, as well as the downstream signal transduction mediated by these receptors. Furthermore, we present the latest clinical and preclinical findings on drugs that target integrins for steatosis, inflammation, fibrosis and NAFLD-related HCC treatment.

摘要

非酒精性脂肪性肝病(NAFLD)是慢性肝病的主要病因,随着全球发病率的上升,它带来了沉重的健康负担。NAFLD涵盖了从肝脂肪变性到非酒精性脂肪性肝炎(NASH)的一系列病症,有可能发展为肝硬化,在严重情况下甚至会发展为肝细胞癌(HCC)。NAFLD不仅仅是简单的代谢紊乱,还涉及多种免疫细胞介导的炎症过程。整合素是一类异二聚体跨膜细胞粘附受体家族,它们调节NAFLD发生和发展的各个方面,包括肝细胞脂肪变性、肝星状细胞(HSC)激活和免疫细胞浸润。在这篇综述中,我们全面总结了整合素在NAFLD中的作用,以及这些受体介导的下游信号转导。此外,我们还介绍了针对整合素治疗脂肪变性、炎症、纤维化和NAFLD相关HCC的药物的最新临床和临床前研究结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72f1/11659783/f665bc2bd55e/ABBS-2024-208-t5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72f1/11659783/65352c743f92/ABBS-2024-208-t1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72f1/11659783/1d25a470dbe2/ABBS-2024-208-t2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72f1/11659783/0e25a191d4cb/ABBS-2024-208-t3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72f1/11659783/71f7a32f7b66/ABBS-2024-208-t4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72f1/11659783/f665bc2bd55e/ABBS-2024-208-t5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72f1/11659783/65352c743f92/ABBS-2024-208-t1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72f1/11659783/1d25a470dbe2/ABBS-2024-208-t2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72f1/11659783/0e25a191d4cb/ABBS-2024-208-t3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72f1/11659783/71f7a32f7b66/ABBS-2024-208-t4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72f1/11659783/f665bc2bd55e/ABBS-2024-208-t5.jpg

相似文献

[1]
Integrins and NAFLD-associated liver diseases: clinical associations, pathophysiological mechanisms and pharmacological implications.

Acta Biochim Biophys Sin (Shanghai). 2024-9-14

[2]
Recent Insight into the Role of Fibrosis in Nonalcoholic Steatohepatitis-Related Hepatocellular Carcinoma.

Int J Mol Sci. 2019-4-9

[3]
Hepatic Stellate Cells: Dictating Outcome in Nonalcoholic Fatty Liver Disease.

Cell Mol Gastroenterol Hepatol. 2023

[4]
The hedgehog pathway in nonalcoholic fatty liver disease.

Crit Rev Biochem Mol Biol. 2018-3-20

[5]
A Scoping Review on Lipocalin-2 and Its Role in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma.

Int J Mol Sci. 2021-3-11

[6]
Gemcabene downregulates inflammatory, lipid-altering and cell-signaling genes in the STAM™ model of NASH.

PLoS One. 2018-5-30

[7]
Role of G Protein-Coupled Receptors in Hepatic Stellate Cells and Approaches to Anti-Fibrotic Treatment of Non-Alcoholic Fatty Liver Disease.

Front Endocrinol (Lausanne). 2021

[8]
Molecular Mechanisms: Connections between Nonalcoholic Fatty Liver Disease, Steatohepatitis and Hepatocellular Carcinoma.

Int J Mol Sci. 2020-2-23

[9]
The Natural Course of Non-Alcoholic Fatty Liver Disease.

Int J Mol Sci. 2016-5-20

[10]
Nonalcoholic Fatty Liver Disease and Staging of Hepatic Fibrosis.

Adv Exp Med Biol. 2024

引用本文的文献

[1]
Nrf2/UBE3B protects against acute lung injury by inhibiting ferritinophagy through the ubiquitination of NCOA4.

Biol Direct. 2025-7-16

[2]
Hepatocyte nuclear factor 4-Alpha: a key regulator in liver carcinogenesis.

Cell Oncol (Dordr). 2025-8

本文引用的文献

[1]
Evaluation of an Integrin αβ Radiotracer, [F]F-FPP-RGD, for Monitoring Pharmacological Effects of Integrin α siRNA in the NASH Liver.

Nucl Med Mol Imaging. 2023-8

[2]
Global burden of liver disease: 2023 update.

J Hepatol. 2023-8

[3]
Challenges and opportunities in NASH drug development.

Nat Med. 2023-3

[4]
Integrins in human hepatocellular carcinoma tumorigenesis and therapy.

Chin Med J (Engl). 2023-2-5

[5]
Targeting integrin pathways: mechanisms and advances in therapy.

Signal Transduct Target Ther. 2023-1-2

[6]
Non-Alcoholic Fatty Liver Disease (NAFLD) Pathogenesis and Natural Products for Prevention and Treatment.

Int J Mol Sci. 2022-12-7

[7]
Pharmacotherapy for Non-alcoholic Fatty Liver Disease Associated with Diabetes Mellitus Type 2.

J Clin Transl Hepatol. 2022-10-28

[8]
CCN1/Integrin αβ Instigates Free Fatty Acid-Induced Hepatocyte Lipid Accumulation and Pyroptosis through NLRP3 Inflammasome Activation.

Nutrients. 2022-9-19

[9]
The interactions between integrin αβ of liver cancer cells and fibronectin of fibroblasts promote tumor growth and angiogenesis.

Int J Biol Sci. 2022

[10]
The Crosstalk Between Liver Sinusoidal Endothelial Cells and Hepatic Microenvironment in NASH Related Liver Fibrosis.

Front Immunol. 2022

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