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Int J Clin Exp Pathol 2013;6(4):571-585

Original Article
Human fetal ductal plate revisited: II. MUC1, MUC5AC, and MUC6 are expressed in
human fetal ductal plate and MUC1 is expressed also in remodeling ductal plate,
remodeled ductal plate and mature bile ducts of human fetal livers

Tadashi Terada

Departments of Pathology, Shizuoka City Shimizu Hospital, Shizuoka, Japan

Received January 6, 2013; Accepted February 15, 2013; Epub March 15, 2013; Published April 1, 2013

Abstract: 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. (IJCEP1301013).

Keywords: Ductal plate, human fetal liver, intrahepatic bile duct development, mucins, MUC apomucins, histochemistry, immunohistochemistry

Address correspondence to: Dr. Tadashi Terada, Department of Pathology, Shizuoka City Shimizu Hospital, Miyakami 1231 Shimizu-Ku,
Shi-zuoka 424-8636, Japan. Tel: +81-54-336-1111; Fax: +81-54-334-1173; E-mail: piyo0111jp@yahoo.co.jp