Participation of peribiliary glands in biliary tract pathophysiologies

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). ORIGINAL ARTICLE 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. 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 be central to normal tissue turnover and injury repair, and may play key roles in the pathophysiology of several biliary tract diseases [12] . In hepatolithiasis, the peribiliary glands proliferate markedly, secrete large amounts of mucin into the bile duct lumen [14,15] and may be involved in stone fo...

Progenitor cell niches in the human pancreatic duct system and associated pancreatic duct glands: an anatomical and immunophenotyping study

“…; Igarashi et al. ), but our results also suggest that PDGs are candidate sites of origin of pancreatic intra‐epithelial neoplasias (PanIN) and pancreatic duct adenocarcinomas. Also, in response to injury, PDGs undergo a mucinous metaplasia with PanIN features (Strobel et al.…”

“Biliary Diseases with Pancreatic Counterparts”: Cross-sectional Imaging Findings

“…In IgG4-related sclerosing cholangitis, focal or multifocal biliary strictures are most commonly seen in the distal common bile duct and hilar and central intrahepatic bile ducts. This imaging feature correlates with the abundance of peribiliary glands in these locations at histopathologic examination (5). Patients with type 1 autoimmune pancreatitis may also occasionally demonstrate focal or multifocal pancreatic ductal strictures, ectatic side branches arising from the site of the stricture, and a lack of upstream ductal dilatation (25,26).…”

“…Thus, the biliary tract acts as a conduit for the secretions from the hepatic parenchyma (bile) and from the peribiliary glands. The peribiliary glands can be located within the bile duct wall (intramural type) or the periductal connective tissue (extramural type) (Fig 1) (5,6). Although intramural peribiliary glands are simple tubular mucous glands, extramural peribiliary glands are branched tubuloalveolar seromucous glands.…”

Peribiliary Glands Are Key in Regeneration of the Human Biliary Epithelium After Severe Bile Duct Injury

“…(15) However, over the past decade, PBG cells have been characterized in more detail and stem cell properties of PBG have come to light. (1,3,16,17) Although marked proliferation of PBG in the context of large bile duct pathologies has been described for hepatolithiasis, for primary sclerosing cholangitis, and after ischemia, (4)(5)(6) today's view on PBG and their counterparts in the pancreas and liver suggests that several other hepato-pancreato-biliary diseases are also linked with these progenitor cell compartments. (2,18,19) In support of this, the current ex vivo study demonstrated the central role of PBG in bile duct recovery after severe ischemic damage.…”

“…Up to now, the activation of PBG has been observed in patients with hepatolithiasis, primary sclerosing cholangitis, and posttransplant cholangiopathies. (3)(4)(5)(6) Our understanding of PBG and their behavior in pathological conditions is based on findings in cross-sectional studies, animal studies, and cell cultures. These models have not provided definite proof of the functional and morphological recovery of the biliary epithelial lining by a coordinated response of PBG cells after severe injury of the large bile ducts in humans.…”