Key role of interferon regulatory factor 1 (IRF-1) in regulating liver disease: progress and outlook

Tao CHEN; Shipeng LI; Dewen DENG; Weiye ZHANG; Jianjun ZHANG; Zhongyang SHEN

doi:10.1631/jzus.B2300159

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Review | Updated：2024-06-24

Key role of interferon regulatory factor 1 (IRF-1) in regulating liver disease: progress and outlook
Key role of interferon regulatory factor 1 (IRF-1) in regulating liver disease: progress and outlook
IRF-1在肝脏疾病调控中的关键作用：进展与展望
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 25, Issue 6, Pages: 451-470(2024)
Affiliations：

1.First Central Clinical School, Tianjin Medical University, Tianjin 300192, China
2.Department of Organ Transplant, Tianjin First Central Hospital, Tianjin 300192, China
3.Research Institute of Transplant Medicine, Nankai University, Tianjin 300192, China
4.Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, Zhengzhou 450000, China
5.Key Laboratory of Organ Transplant, Tianjin First Central Hospital, Tianjin 300192, China
Funds：
DOI：10.1631/jzus.B2300159
CLC：
CSTR：
Published： 15 June 2024 ，

Received： 15 March 2023 ，

Revised： 01 September 2023 ，

陈涛,李世朋,邓德文等.IRF-1在肝脏疾病调控中的关键作用：进展与展望[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(06):451-470.

Tao CHEN, Shipeng LI, Dewen DENG, et al. Key role of interferon regulatory factor 1 (IRF-1) in regulating liver disease: progress and outlook. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(6):451-470(2024)
陈涛,李世朋,邓德文等.IRF-1在肝脏疾病调控中的关键作用：进展与展望[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(06):451-470. DOI： 10.1631/jzus.B2300159.

Tao CHEN, Shipeng LI, Dewen DENG, et al. Key role of interferon regulatory factor 1 (IRF-1) in regulating liver disease: progress and outlook. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(6):451-470(2024) DOI： 10.1631/jzus.B2300159.

摘要

干扰素调节因子1（IRF-1）是干扰素调节因子家族的重要一员，其主要功能是能够与靶基因上的干扰素刺激反应元件（ISRE）结合，进而在干扰素诱导的信号通路中发挥重要作用。IRF-1作为一种重要的转录因子，在细胞周期调控、细胞死亡信号转导、增强免疫监视等方面具有重要作用。当前研究表明，IRF-1在多种肝脏疾病的发生和发展中发挥至关重要的作用，包括抑制肝炎病的复制、缓解肝纤维化的进展和加重肝缺血再灌注损伤（HIRI）等。IRF-1还作为一种重要的肿瘤抑制因子，在临床上可作为预测肝癌预后和复发的潜在指标。此外，最新的研究还揭示了IRF-1在介导其他肝脏疾病中的潜在作用，如预防酒精性/非酒精性脂肪性肝病，抑制胆管细胞癌的生物学进展，预防细胞排斥反应等。虽然当前的研究极少涉及IRF-1的临床转化领域，但几种化合物和药物似乎可以通过激活IRF-1信号通路，在动物体特定肝脏疾病模型中发挥保护功能。在本文中，我们将综述既往文献以帮助解读IRF-1在肝脏疾病治疗中的研究进展，并提供未来转化医学应用的理论基础。

Abstract

Interferon regulatory factor 1 (IRF-1) is a member of the IRF family. It is the first transcription factor to be identified that could bind to the interferon-stimulated response element (ISRE) on the target gene and displays crucial roles in the interferon-induced signals and pathways. IRF-1

as an important medium

has all of the advantages of full cell cycle regulation

cell death signaling transduction

and reinforcing immune surveillance

which are well documented. Current studies indicate that IRF-1 is of vital importance to the occurrence and evolution of multifarious liver diseases

including but not limited to inhibiting the replication of the hepatitis virus (A/B/C/E)

alleviating the progression of liver fibrosis

and aggravating hepatic ischemia-reperfusion injury (HIRI). The tumor suppression of IRF-1 is related to the clinical characteristics of liver cancer patients

which makes it a potential indicator for predicting the prognosis and recurrence of liver cancer; additionally

the latest studies have revealed other effects of IRF-1 such as protection against alcoholic/non-alcoholic fatty liver disease (AFLD/NAFLD)

cholangiocarcinoma suppression

and uncommon traits in other liver diseases that had previously received little attention. Intriguingly

several compounds and drugs have featured a protective function in specific liver disease models in which there is significant involvement of the IRF-1 signal. In this paper

we hope to propose a prospective research basis upon which to help decipher translational medicine applications of IRF-1 in liver disease treatment.

关键词

干扰素调节因子1（IRF-1）肝炎病毒肝纤维化肝缺血再灌注损伤（HIRI）肝癌

Keywords

Interferon regulatory factor (IRF-1)Hepatitis virusLiver fibrosisHepatic ischemia-reperfusion injury (HIRI)Liver cancer

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