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黏液素2在腹膜假黏液瘤中的生物合成及功能

The Biological Synthesis and the Function of Mucin 2 in Pseudomyxoma Peritonei.

作者信息

Lin Yu-Lin, Li Yan

机构信息

Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University (Beijing Technical Training Base of Tumor Deep Hyperthermia and Whole-Body Hyperthermia), Department of Oncology, Capital Medical University, Beijing, 100038, People's Republic of China.

出版信息

Cancer Manag Res. 2021 Oct 15;13:7909-7917. doi: 10.2147/CMAR.S324982. eCollection 2021.

Abstract

Excessive mucus secretion is the most prominent feature of pseudomyxoma peritonei (PMP), which often leads to significant increase in abdominal circumference, intractable abdominal pain, progressive intestinal obstruction, abdominal organ adhesions, and cachexia. Excessive mucus secretion is also the main cause of death. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the recommended treatment for PMP. However, recurrence is frequently observed even after CRS and HIPEC, presenting similar clinical manifestations. Mucin 2 (MUC2) is the main type of mucin in PMP and plays a key role in the progressive sclerosis of mucus. To comprehensively demonstrate the biosynthetic process and molecular features of MUC2 and to provide new directions for the development of PMP mucolytic strategies, this review systematically summarizes the molecular biology of MUC2, including gene structure, transcription, translation, post-translational modification, tertiary structure, and factors regulating mucus viscoelasticity. The results show that MUC2 is a highly glycosylated protein, with glycan accounts for 80% to 90% of the dry weight. The assembly pattern of MUC2 is highly complicated, presenting a bead-like filament. Salt concentration, pH, mucin concentration and trefoil factor family may contribute to the increase in mucus viscoelasticity and sclerosis, which could be used to develop drugs to soften or even dissolve mucus in the future.

摘要

黏液分泌过多是腹膜假黏液瘤(PMP)最突出的特征,常导致腹围显著增加、顽固性腹痛、进行性肠梗阻、腹部器官粘连和恶病质。黏液分泌过多也是主要的死亡原因。细胞减灭术(CRS)联合腹腔内热灌注化疗(HIPEC)是PMP的推荐治疗方法。然而,即使在CRS和HIPEC后仍经常观察到复发,表现出相似的临床表现。黏蛋白2(MUC2)是PMP中主要的黏蛋白类型,在黏液的进行性硬化中起关键作用。为了全面阐述MUC2的生物合成过程和分子特征,并为PMP黏液溶解策略的开发提供新方向,本综述系统总结了MUC2的分子生物学,包括基因结构、转录、翻译、翻译后修饰、三级结构以及调节黏液黏弹性的因素。结果表明,MUC2是一种高度糖基化的蛋白质,聚糖占干重的80%至90%。MUC2的组装模式高度复杂,呈珠状细丝。盐浓度、pH值、黏蛋白浓度和三叶因子家族可能导致黏液黏弹性增加和硬化,这可为未来开发软化甚至溶解黏液的药物提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/711b/8527350/1da8585f48d2/CMAR-13-7909-g0001.jpg

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