{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:39:08Z","timestamp":1791405548006,"version":"4.3.3"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":700,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>Peribiliary glands (PBGs) are clusters of epithelial cells residing in the submucosal compartment of extrahepatic bile ducts (EHBDs). Though their function is largely undefined, they may represent a stem cell niche. Here, we hypothesized that PBGs are populated by mature and undifferentiated cells capable of proliferation in pathological states. To address this hypothesis, we developed a novel whole-mount immunostaining assay that preserves the anatomical integrity of EHBDs coupled with confocal microscopy and found that PBGs populate the entire length of the extrahepatic biliary tract, except the gallbladder. Notably, in addition to the typical position of PBGs adjacent to the duct mucosa, PBGs elongate and form intricate intramural epithelial networks that communicate between different segments of the bile duct mucosa. Network formation begins where the cystic duct combines with hepatic ducts to form the common bile duct (CBD) and continues along the CBD. Cells of PBGs and the peribiliary network stain positively for \u03b1-tubulin, mucins, and chromogranin A, as well as for endoderm transcription factors SRY (sex determining region Y)-box 17 and pancreatic and duodenal homeobox 1, and proliferate robustly subsequent to duct injury induced by virus infection and bile duct ligation.<\/jats:bold>\n                      <jats:bold>Conclusion<\/jats:bold>\n                      <jats:bold>: PBGs form elaborate epithelial networks within the walls of EHBDs, contain cells of mature and immature phenotypes, and proliferate in response to bile duct injury. The anatomical organization of the epithelial network in tubules and the link with PBGs support an expanded cellular reservoir with the potential to restore the integrity and function of the bile duct mucosa in diseased states. (Hepatology 2013;58:1486\u20131496)<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.26485","type":"journal-article","created":{"date-parts":[[2013,5,22]],"date-time":"2013-05-22T08:57:02Z","timestamp":1369213022000},"page":"1486-1496","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":77,"title":["Identification of intramural epithelial networks linked to peribiliary glands that express progenitor cell markers and proliferate after injury in mice"],"prefix":"10.1097","volume":"58","author":[{"given":"Frank","family":"DiPaola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranavkumar","family":"Shivakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Pfister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Walters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg","family":"Sabla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge A.","family":"Bezerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-33-20241201","doi-asserted-by":"crossref","first-page":"6279","DOI":"10.1053\/j.gastro.2009.03.035","article-title":"Mechanisms of liver development: concepts for understanding liver disorders and design of novel therapies.","volume":"137","author":"Lemaigre","year":"2009","journal-title":"Gastroenterology"},{"key":"R2-33-20241201","doi-asserted-by":"crossref","first-page":"105121","DOI":"10.1586\/egh.10.87","article-title":"Advances in the regulation of liver regeneration.","volume":"5","author":"Jia","year":"2011","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"R3-33-20241201","doi-asserted-by":"crossref","first-page":"257264","DOI":"10.1016\/j.biocel.2010.06.020","article-title":"Molecular mechanisms of bile duct development.","volume":"43","author":"Zong","year":"2011","journal-title":"Int J Biochem Cell Biol"},{"key":"R4-33-20241201","doi-asserted-by":"crossref","first-page":"372378","DOI":"10.1002\/hep.510300223","article-title":"Anomalous development of the hepatobiliary system in the Inv mouse.","volume":"30","author":"Mazziotti","year":"1999","journal-title":"Hepatology"},{"key":"R5-33-20241201","doi-asserted-by":"crossref","first-page":"1236912374","DOI":"10.1074\/jbc.M112162200","article-title":"Haploinsufficiency of the mouse Forkhead Box f1 gene causes defects in gall bladder development.","volume":"277","author":"Kalinichenko","year":"2002","journal-title":"J Biol Chem"},{"key":"R6-33-20241201","doi-asserted-by":"crossref","first-page":"9931000","DOI":"10.1002\/dvdy.21900","article-title":"Defective development of the gall bladder and cystic duct in Lgr4hypomorphic mice.","volume":"238","author":"Yamashita","year":"2009","journal-title":"Dev Dyn"},{"key":"R7-33-20241201","doi-asserted-by":"crossref","first-page":"8387","DOI":"10.1038\/ng1273","article-title":"Conversion of biliary system to pancreatic tissue in Hes1deficient mice.","volume":"36","author":"Sumazaki","year":"2004","journal-title":"Nat Genet"},{"key":"R8-33-20241201","doi-asserted-by":"crossref","first-page":"21592172","DOI":"10.1002\/hep.24590","article-title":"Multipotent stemprogenitor cells in human biliary tree give rise to hepatocytes, cholangiocytes, and pancreatic islets.","volume":"54","author":"Cardinale","year":"2011","journal-title":"Hepatology"},{"key":"R9-33-20241201","doi-asserted-by":"crossref","first-page":"584597","DOI":"10.1097\/00000658-192510010-00005","article-title":"Observations on the histologic and pathologic anatomy of the hepatic, cystic, and common bile ducts.","volume":"82","author":"Burden","year":"1925","journal-title":"Ann Surg"},{"key":"R10-33-20241201","doi-asserted-by":"crossref","first-page":"213220","DOI":"10.1002\/path.1711280407","article-title":"The development of the glands of the common bile duct.","volume":"128","author":"Spitz","year":"1979","journal-title":"J Pathol"},{"key":"R11-33-20241201","doi-asserted-by":"crossref","first-page":"7579","DOI":"10.1111\/j.1440-1746.1994.tb01220.x","article-title":"Intrahepatic peribiliary glands of humans. 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