Terada Tadashi
Department of Pathology, Shizuoka City Shimizu Hospital, Shizuoka, Japan.
Int J Clin Exp Pathol. 2013;6(4):571-85. Epub 2013 Mar 15.
Mucins are high-molecular-weight glycoproteins, which are heavily decorated with a large number of O-linked oligosaccharides and a few N-glycan chains, linked to a protein backbone. The protein backbone is called mucin core protein or MUC apomucins. MUC expression is down-regulated or up-regulated in malignant neoplasms. These alterations of MUC apomucins, which are regulated by MUC genes, are associated with carcinogenesis and malignant potentials of cancers. MUC expression during human fetal intrahepatic bile duct (IBD) development has been studied only once, and there has been only one histochemical study of mucins in human fetal IBD development. The author herein immunohistochemically investigated the expression of MUC1, MUC2, MUC5AC, and MUC6, and histochemically investigated carbohydrate component of mucins in human fetal cholangiocytes with the use of 32 human fetal livers of various gestational ages. MUC1 is a transmembranous apomucin, while MUC2, MUC5AC and MUC6 are secretory apomucins. Under normal conditions, MUC1 (polymorphic epithelial mucin) is present mainly in the pancreatic epithelium. MUC2 (goblet cell mucin) is mainly located in goblet cells. MUC5AC (gastric foveolar mucin) and MUC6 (pyloric gland-type mucin) are located in the stomach. In the present study, the processes of the human IBD development could be categorized into four stages; ductal plate (DP), remodeling DP, remodeled DP, and mature IBDs. The author identified that MUC1 was present in ductal plate (DP), remodeling DP, remodeled DP, and mature IBD in human fetal livers. MUC5AC and MUC6 were present only in the DP. MUC5AC and MUC6 were absent in remodeling DP, remodeled DP, and mature IBD in human fetal livers. No expression of MUC2 was seen throughout the fetal IBD development. Histochemically, no carbohydrate component of mucins were seen in the remodeling DP and remodeled DP, while neutral and acidic mucins (carboxylated and sulfated mucins) were seen in mature IBD in human fetal livers. The DP showed frequently neutral mucins and less frequently acidic mucins (carboxylated and sulfated mucins residues). These findings suggest that the DP cells have MUC1, MUC5AC and MUC6, and that remodeling DP, remodeled DP, and mature IBDs have MUC1, but not MUC5AC and MUC6. The presence of neutral and acidic carbohydrates in DP suggests that these carbohydrates of mucin are attached to the MUC5AC and MUC6 mucin core proteins. Although the implications are unclear, the expression of these MUC apomucins and their carbohydrate residues are associated with normal development of IBDs in human fetal livers.
黏蛋白是高分子量糖蛋白，其大量被O-连接寡糖和少数N-聚糖链修饰，并连接到蛋白质主链上。该蛋白质主链称为黏蛋白核心蛋白或MUC脱辅基黏蛋白。MUC在恶性肿瘤中表达下调或上调。这些受MUC基因调控的MUC脱辅基黏蛋白的改变与癌症的发生和恶性潜能相关。人类胎儿肝内胆管（IBD）发育过程中MUC的表达仅被研究过一次，并且关于人类胎儿IBD发育中黏蛋白的组织化学研究也仅有一项。本文作者利用32例不同胎龄的人类胎儿肝脏，通过免疫组织化学方法研究了MUC1、MUC2、MUC5AC和MUC6的表达，并通过组织化学方法研究了人类胎儿胆管细胞中黏蛋白的碳水化合物成分。MUC1是一种跨膜脱辅基黏蛋白，而MUC2、MUC5AC和MUC6是分泌性脱辅基黏蛋白。在正常情况下，MUC1（多形性上皮黏蛋白）主要存在于胰腺上皮中。MUC2（杯状细胞黏蛋白）主要位于杯状细胞中。MUC5AC（胃小凹黏蛋白）和MUC6（幽门腺型黏蛋白）位于胃中。在本研究中，人类IBD发育过程可分为四个阶段：导管板（DP）、重塑DP、重塑后的DP和成熟IBD。作者发现MUC1存在于人类胎儿肝脏的导管板（DP）、重塑DP、重塑后的DP和成熟IBD中。MUC5AC和MUC6仅存在于DP中。在人类胎儿肝脏的重塑DP、重塑后的DP和成熟IBD中不存在MUC5AC和MUC6。在整个胎儿IBD发育过程中均未观察到MUC2的表达。组织化学研究发现，在重塑DP和重塑后的DP中未观察到黏蛋白的碳水化合物成分，而在人类胎儿肝脏的成熟IBD中观察到中性和酸性黏蛋白（羧化和硫酸化黏蛋白）。DP中常见中性黏蛋白，较少见酸性黏蛋白（羧化和硫酸化黏蛋白残基）。这些发现表明，DP细胞具有MUC1、MUC5AC和MUC6，而重塑DP、重塑后的DP和成熟IBD具有MUC1，但不具有MUC5AC和MUC6。DP中存在中性和酸性碳水化合物表明这些黏蛋白的碳水化合物与MUC5AC和MUC6黏蛋白核心蛋白相连。尽管其意义尚不清楚，但这些MUC脱辅基黏蛋白及其碳水化合物残基的表达与人类胎儿肝脏中IBD的正常发育相关。
