干扰素调节因子在非酒精性脂肪肝和非酒精性脂性肝炎中的作用

IF 1.5 Q3 GASTROENTEROLOGY & HEPATOLOGY
Chunye Zhang, Shuai Liu, Ming Yang
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引用次数: 6

摘要

非酒精性脂肪肝(NAFLD)正成为最常见的慢性肝病,并伴有许多代谢合并症,如肥胖、糖尿病和心血管疾病。非酒精性脂肪性肝炎(NASH)是NAFLD的一种晚期形式,伴随着肝脂肪变性、炎症、细胞死亡和不同程度的肝纤维化的进展。干扰素(IFN)已被证明在NAFLD和NASH的发病机制中发挥重要作用。它们的调节转录因子,如干扰素调节因子(IRFs),可以调节IFN的表达,以及参与巨噬细胞极化的基因,这些基因与NAFLD和晚期肝病的发病机制有关。本文综述了IRF相关信号通路在肝脏炎症、胰岛素抵抗和免疫细胞激活中的作用。IRF如IRF1和IRF4也参与巨噬细胞的极化,这在NAFLD或NASH发病机制中起着关键作用。此外,IRF已被证明受到包括微小RNA、PPAR调节剂、抗炎剂和TLR激动剂或拮抗剂在内的治疗的调节。在慢性肝病中通过这些治疗调节IRF介导的因子可以改善NAFLD向NASH的进展。此外,腺病毒和CRISPR激活质粒也可用于调节慢性肝病中IRF介导的作用。评估IRF调节因子在NAFLD治疗中的临床前和临床试验对未来的方向至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Role of Interferon Regulatory Factors in Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis
Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease with many metabolic comorbidities, such as obesity, diabetes, and cardiovascular diseases. Non-alcoholic steatohepatitis (NASH), an advanced form of NAFLD, accompanies the progression of hepatic steatosis, inflammation, cell death, and varying degree of liver fibrosis. Interferons (IFNs) have been shown to play important roles in the pathogenesis of NAFLD and NASH. Their regulating transcriptional factors such as interferon regulatory factors (IRFs) can regulate IFN expression, as well as genes involved in macrophage polarization, which are implicated in the pathogenesis of NAFLD and advanced liver disease. In this review, the roles of IRF-involved signaling pathways in hepatic inflammation, insulin resistance, and immune cell activation are reviewed. IRFs such as IRF1 and IRF4 are also involved in the polarization of macrophages that contribute to critical roles in NAFLD or NASH pathogenesis. In addition, IRFs have been shown to be regulated by treatments including microRNAs, PPAR modulators, anti-inflammatory agents, and TLR agonists or antagonists. Modulating IRF-mediated factors through these treatments in chronic liver disease can ameliorate the progression of NAFLD to NASH. Furthermore, adenoviruses and CRISPR activation plasmids can also be applied to regulate IRF-mediated effects in chronic liver disease. Pre-clinical and clinical trials for evaluating IRF regulators in NAFLD treatment are essential in the future direction.
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来源期刊
Gastroenterology Insights
Gastroenterology Insights GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
2.80
自引率
3.40%
发文量
35
审稿时长
10 weeks
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