Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Hepatol. Aug 27, 2013; 5(8): 425-432
Published online Aug 27, 2013. doi: 10.4254/wjh.v5.i8.425
Participation of peribiliary glands in biliary tract pathophysiologies
Saya Igarashi, Yasunori Sato, Xiang Shan Ren, Kenichi Harada, Motoko Sasaki, Yasuni Nakanuma
Saya Igarashi, Yasunori Sato, Xiang Shan Ren, Kenichi Harada, Motoko Sasaki, Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan
Author contributions: Igarashi S, Sato Y and Ren XS performed the majority of experiments; Harada K and Sasaki M provided vital reagents and advice; Nakanuma Y supervised this study and wrote the manuscript.
Correspondence to: Yasuni Nakanuma, MD, Department of Human Pathology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8640, Japan. nakanuma@staff.kanazawa-u.ac.jp
Telephone: +81-76-2652197 Fax: +81-76-2344229
Received: May 2, 2013
Revised: July 24, 2013
Accepted: August 4, 2013
Published online: August 27, 2013
Abstract

AIM: To investigate the roles of peribiliary glands around the bile ducts in the pathophysiology of the biliary tract.

METHODS: The expression of fetal pancreatic markers, pancreatic duodenal homeobox factor 1 (PDX1) and hairy and enhancer of split 1 (HES1) and endodermal stem/progenitor (S/P) cell markers [CD44s, chemokine receptor type 4 (CXCR4), SOX9 and epithelial cell adhesion molecule (EpCAM)] were examined immunohistochemically in 32 normal adult livers (autopsy livers) and 22 hepatolithiatic livers (surgically resected livers). The latter was characterized by the proliferation of the peribiliary glands. Immunohistochemistry was performed using formalin-fixed, paraffin-embedded tissue sections after deparaffinization. Although PDX1 and HES1 were expressed in both the nucleus and cytoplasm of epithelial cells, only nuclear staining was evaluated. SOX9 was expressed in the nucleus, while CD44s, CXCR4 and EpCAM were expressed in the cell membranes. The frequency and extent of the expression of these molecules in the lining epithelia and peribiliary glands were evaluated semi-quantitatively based on the percentage of positive cells: 0, 1+ (focal), 2+ (moderate) and 3+ (extensive).

RESULTS: In normal livers, PDX1 was infrequently expressed in the lining epithelia, but was frequently expressed in the peribiliary glands. In contrast, HES1 was frequently expressed in the lining epithelia, but its expression in the peribiliary glands was focal, suggesting that the peribiliary glands retain the potential of differentiation toward the pancreas and the lining epithelia exhibit properties to inhibit such differentiation. This unique combination was also seen in hepatolithiatic livers. The expression of endodermal S/P cell markers varied in the peribiliary glands in normal livers: SOX9 and EpCAM were frequently expressed, CD44s infrequently, and CXCR4 almost not at all. The expression of these markers, particularly CD44s and CXCR4, increased in the peribiliary glands and lining epithelia in hepatolithiatic livers. This increased expression of endodermal S/P cell markers may be related to the increased production of intestinal and gastric mucin and also to the biliary neoplasia associated with the gastric and intestinal phenotypes reported in hepatolithiasis.

CONCLUSION: The unique expression pattern of PDX1 and HES1 and increased expression of endodermal S/P cell markers in the peribiliary glands may be involved in biliary pathophysiologies.

Keywords: Biliary tree, Peribiliary glands, Pancreatic duodenal homeobox factor 1, Stem cells, Differentiation, Pancreas

Core tip: Immunohistochemical analysis showed that pancreatic duodenal homeobox factor 1 was more frequently expressed in the peribiliary glands than epithelia lining the bile duct and was accompanied by the reciprocal expression pattern of hairy and enhancer of split 1. These results may reflect maintenance of the biliary tract and the increased expression of endodermal stem/progenitor cell markers may be involved in the unique pathophysiologies of the peribiliary glands.