阐明半乳糖凝集素-3在原发性硬化性胆管炎肝移植后复发中的作用,作为一个潜在的治疗靶点。

IF 3.3 4区 医学 Q3 CHEMISTRY, MEDICINAL
Rozita Khodashahi, Asieh Hatefi Olaee, Gordon A Ferns, Mohsen Aliakbarian, Mohammad-Hassan Arjmand
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引用次数: 0

摘要

原发性硬化性胆管炎(PSC)发生在肝移植(LT)后约25%的患者中,并与显著的发病率和死亡率相关。复发性PSC后的肝管胆汁淤积可能导致肝硬化的发展和肝脏再移植的需要。迄今为止,肝移植后PSC复发的确切病因尚不清楚,目前也无法预测哪些患者有PSC复发的风险。细胞外半乳糖凝集素-3 (Gal-3)作为损伤相关分子模式(DAMP)被损伤的肝细胞释放到细胞外基质(ECM)中。Gal-3通过结合和交联中性粒细胞和巨噬细胞表面蛋白,促进免疫细胞向损伤部位趋化,激活巨噬细胞炎性体复合物,在免疫应答和炎症反应中发挥重要作用。此外,Gal-3通过激活肝卫星细胞(HSC)为肌成纤维细胞表型,诱导转化生长因子β (TGF-β)等促纤维化分子,增加ECM中胶原的表达,导致肝纤维化。有证据表明,靶向Gal-3可能在预防PSC复发进展和lt后胆汁淤积进展方面具有重要的治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Elucidating the Role of Galectin-3 in the Recurrence of Primary Sclerosing Cholangitis Post-Liver Transplantation as a Potential Therapeutic Target.

Primary sclerosing cholangitis (PSC) occurs in approximately 25% of patients post-liver transplantation (LT) and is associated with significant morbidity and mortality. Hepatic duct cholestasis following recurrent PSC may lead to the development of liver cirrhosis and the need for liver retransplantation. To date, the exact etiology of the recurrence of PSC post-LT remains unknown, and it is not currently possible to predict which patients are at risk for recurrence of PSC. Extracellular Galectin-3 (Gal-3) acts as a damage-associated molecular pattern (DAMP) when released into the extracellular matrix (ECM) by injured liver cells. Gal-3 plays a crucial role in immune responses and inflammation by binding and cross-linking surface proteins of neutrophils and macrophages, facilitating the chemotaxis of immune cells to the site of injury, and activating the macrophage inflammasome complex. In addition, Gal-3, by activation of hepatic satellite cells (HSC) to myofibroblast phenotype, induces profibrotic molecules, such as transforming growth factor beta (TGF-β) and increases the expression of collagens in the ECM, leading to liver fibrogenesis. According to the evidence, targeting Gal-3 may have important therapeutic potential in preventing the progression of recurrence in PSC and cholestatic progression post-LT.

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来源期刊
CiteScore
6.40
自引率
2.90%
发文量
186
审稿时长
3-8 weeks
期刊介绍: Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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