IL-22治疗酒精相关肝病及其他疾病的最新进展

IF 4.7 2区 医学 Q1 PATHOLOGY
Lihong Fu, Burhan Yokus, Bin Gao, Pal Pacher
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引用次数: 0

摘要

过量饮酒可导致酒精相关性肝病(ALD)的发生,包括脂肪性肝炎、肝硬化和肝细胞癌,以及肝肾综合征等相关并发症。肝细胞死亡、炎症和肝脏再生受损是ALD发病和进展的关键过程。尽管进行了广泛的研究,但治疗ALD的选择仍然有限。IL-22已成为一个有希望的治疗靶点,因为它通过激活STAT3信号通路介导的肝保护特性。IL-22通过减轻凋亡、氧化应激和炎症来提高肝细胞存活率,同时通过肝细胞和肝祖细胞的增殖以及生长因子的上调来促进肝脏再生。此外,IL-22对ALD及其相关并发症影响的各器官上皮细胞具有保护作用。IL-22激动剂(如F-652和UTTR1147A)的临床前模型和早期临床试验研究显示出良好的安全性,良好的耐受性,以及减少肝损伤和促进肝再生的令人鼓舞的疗效。然而,ALD的异质性和多因子性仍面临挑战。需要进一步的研究来优化基于il -22的治疗方法,并阐明它们在ALD管理的综合方法中的作用。本文综述了目前对IL-22生物学及其在ALD病理生理和ALD相关并发症中的作用的认识,以及IL-22的治疗应用、潜在益处和局限性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An Update on IL-22 Therapies in Alcohol-Associated Liver Disease and Beyond.

Excessive alcohol consumption drives the development of alcohol-associated liver disease (ALD), including steatohepatitis, cirrhosis, and hepatocellular carcinoma, and its associated complications, such as hepatorenal syndrome. Hepatocyte death, inflammation, and impaired liver regeneration are key processes implicated in the pathogenesis and progression of ALD. Despite extensive research, therapeutic options for ALD remain limited. IL-22 has emerged as a promising therapeutic target because of its hepatoprotective properties mediated through the activation of the STAT3 signaling pathway. IL-22 enhances hepatocyte survival by mitigating apoptosis, oxidative stress, and inflammation while simultaneously promoting liver regeneration through the proliferation of hepatocytes and hepatic progenitor cells and the up-regulation of growth factors. Additionally, IL-22 exerts protective effects on epithelial cells in various organs affected by ALD and its associated complications. Studies from preclinical models and early-phase clinical trials of IL-22 agonists, such as F-652 and UTTR1147A, have shown favorable safety profiles, good tolerability, and encouraging efficacy in reducing liver injury and promoting regeneration. However, the heterogeneity and multifactorial nature of ALD present ongoing challenges. Further research is needed to optimize IL-22-based therapies and clarify their roles within a comprehensive approach to ALD management. This review summarizes the current understanding of IL-22 biology and its role in ALD pathophysiology and ALD-associated complications along with therapeutic application of IL-22, potential benefits, and limitations.

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来源期刊
CiteScore
11.40
自引率
0.00%
发文量
178
审稿时长
30 days
期刊介绍: The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.
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