TY - JOUR
T1 - Hepatobiliary acid-base homeostasis
T2 - Insights from analogous secretory epithelia
AU - Trampert, David C
AU - van de Graaf, Stan F J
AU - Jongejan, Aldo
AU - Oude Elferink, Ronald P J
AU - Beuers, Ulrich
N1 - Funding Information: This work was supported by an Amsterdam UMC , AMC PhD Scholarship (to DT) and a South-African PSC Patient Foundation (to UB). DT, SvdG, AJ and ROE have nothing to disclose. UB received grant support via Amsterdam UMC for investigator-initiated studies from Dr. Falk GmbH (Freiburg) and Intercept (San Diego), and lecture fees from Abbvie, Falk Foundation, Gilead and Intercept. Publisher Copyright: © 2020 European Association for the Study of the Liver Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - Many epithelia secrete bicarbonate-rich fluid to generate flow, alter viscosity, control pH and potentially protect luminal and intracellular structures from chemical stress. Bicarbonate is a key component of human bile and impaired biliary bicarbonate secretion is associated with liver damage. Major efforts have been undertaken to gain insight into acid-base homeostasis in cholangiocytes and more can be learned from analogous secretory epithelia. Extrahepatic examples include salivary and pancreatic duct cells, duodenocytes, airway and renal epithelial cells. The cellular machinery involved in acid-base homeostasis includes carbonic anhydrase enzymes, transporters of the solute carrier family, and intra- and extracellular pH sensors. This pH-regulatory system is orchestrated by protein-protein interactions, the establishment of an electrochemical gradient across the plasma membrane and bicarbonate sensing of the intra- and extracellular compartment. In this review, we discuss conserved principles identified in analogous secretory epithelia in the light of current knowledge on cholangiocyte physiology. We present a framework for cholangiocellular acid-base homeostasis supported by expression analysis of publicly available single-cell RNA sequencing datasets from human cholangiocytes, which provide insights into the molecular basis of pH homeostasis and dysregulation in the biliary system.
AB - Many epithelia secrete bicarbonate-rich fluid to generate flow, alter viscosity, control pH and potentially protect luminal and intracellular structures from chemical stress. Bicarbonate is a key component of human bile and impaired biliary bicarbonate secretion is associated with liver damage. Major efforts have been undertaken to gain insight into acid-base homeostasis in cholangiocytes and more can be learned from analogous secretory epithelia. Extrahepatic examples include salivary and pancreatic duct cells, duodenocytes, airway and renal epithelial cells. The cellular machinery involved in acid-base homeostasis includes carbonic anhydrase enzymes, transporters of the solute carrier family, and intra- and extracellular pH sensors. This pH-regulatory system is orchestrated by protein-protein interactions, the establishment of an electrochemical gradient across the plasma membrane and bicarbonate sensing of the intra- and extracellular compartment. In this review, we discuss conserved principles identified in analogous secretory epithelia in the light of current knowledge on cholangiocyte physiology. We present a framework for cholangiocellular acid-base homeostasis supported by expression analysis of publicly available single-cell RNA sequencing datasets from human cholangiocytes, which provide insights into the molecular basis of pH homeostasis and dysregulation in the biliary system.
KW - Bile acid sensitive ion channel
KW - Carbonic anhydrase
KW - Cholestasis
KW - SLC transporter
KW - Secretory epithelia
KW - Type 5 protein tyrosine phosphatase receptor
UR - http://www.scopus.com/inward/record.url?scp=85097882278&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jhep.2020.10.010
DO - https://doi.org/10.1016/j.jhep.2020.10.010
M3 - Review article
C2 - 33342564
SN - 0168-8278
VL - 74
SP - 428
EP - 441
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 2
ER -