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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

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

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.

Key words: Interferon regulatory factor (IRF-1); Hepatitis virus; Liver fibrosis; Hepatic ischemia-reperfusion injury (HIRI); Liver cancer

Chinese Summary  <2> IRF-1在肝脏疾病调控中的关键作用:进展与展望

陈涛1,李世朋4,邓德文1,5,张玮晔2,3,张建军2,沈中阳2,3,5
1天津医科大学第一中心临床学院,中国天津市,300192
2天津市第一中心医院器官移植科,中国天津市,300192
3南开大学移植医学研究院,中国天津市,300192
4河南省人民医院肝胆外科,中国郑州市,450000
5天津市第一中心医院器官移植重点实验室,中国天津市,300192
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。

关键词组: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


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DOI:

10.1631/jzus.B2300159

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On-line Access:

2024-06-24

Received:

2023-03-15

Revision Accepted:

2023-09-01

Crosschecked:

2024-06-24

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