Publication

Innervation of the proximal human biliary tree

Zanchi, A., Reidy, J., Feldman, H. J., Qualter, J., Gouw, A. S., Osbeck, J., Kofman, A., Balabaud, C., Bioulac-Sage, P., Tiniakos, D. G. & Theise, N. D., 28-Jan-2020, In : Virchows Archiv. 477, 3, p. 385-392 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

Copy link to clipboard

Documents

  • Innervation of the proximal human biliary tree

    Final publisher's version, 1.25 MB, PDF document

    Request copy

DOI

  • Antonela Zanchi
  • Jason Reidy
  • Henry J. Feldman
  • John Qualter
  • Annette S. Gouw
  • Jon Osbeck
  • Alex Kofman
  • Charles Balabaud
  • Paulette Bioulac-Sage
  • Dina G. Tiniakos
  • Neil D. Theise

The autonomic nervous system plays a role in a variety of liver regenerative and metabolic functions, including modulating bile secretion and cholangiocyte and hepatobiliary progenitors of the canals of Hering. However, the nature and location of nerves which link to the proximal biliary tree have remained uncertain. We investigate the anatomic relationship of nerves to the proximal biliary tree including the putative stem/progenitor cell niche of the canal of Hering. Using double immunostaining (fluorescence, histochemistry) to highlight markers of cholangiocytes (biliary-type keratins), nerves (S100, neurofilament protein, PGP9.5, tyrosine hydroxylase), and stellate cells (CRBP-1), we examined sections from normal adult livers from autopsy or surgical resections. There is extensive contact between nerves and interlobular bile ducts, bile ductules, and canals of Hering (CoH). In multiple serial sections from 4 normal livers, biliary-nerve contacts were seen in all of these structures and were more common in the interlobular bile ducts (78/137; 57%) than in the ductules and CoH (95/294; 33%) (p <0.001). Contacts appear to consist of nerves in juxtaposition to the biliary basement membrane, though crossing through basement membrane to interface directly with cholangiocytes is also present. These nerves are positive for tyrosine hydroxylase and are, thus, predominately adrenergic. Electron microscopy confirms nerves closely approximating ductules. Nerve fiber-hepatic stellate cell juxtaposition is observed but without stellate cell approximation to cholangiocytes. We present novel findings of biliary innervation, perhaps mediated in part, by direct cholangiocyte-nerve interactions. The implications of these findings are protean for studies of neuromodulation of biliary physiology and hepatic stem/progenitor cells.

Original languageEnglish
Pages (from-to)385-392
Number of pages8
JournalVirchows Archiv
Volume477
Issue number3
Publication statusPublished - 28-Jan-2020

    Keywords

  • Bile ducts, Nerves, Canals of Hering, Ductules, Stellate cells, BINDING PROTEIN-1 EXPRESSION, HEPATIC PROGENITOR CELLS, NERVOUS-SYSTEM, HUMAN LIVER, STELLATE CELLS, STEM-CELLS, OVAL CELLS, NERVES, DENERVATION, TRANSPLANTATION

ID: 132708700