TY - JOUR
T1 - Role of Bile Acids and the Biliary HCO3 − Umbrella in the Pathogenesis of Primary Biliary Cholangitis
AU - van Niekerk, Jorrit
AU - Kersten, Remco
AU - Beuers, Ulrich
PY - 2018
Y1 - 2018
N2 - The biliary HCO3 − umbrella hypothesis states that human cholangiocytes and hepatocytes create a protective apical alkaline barrier against millimolar concentrations of potentially toxic glycine-conjugated bile salts in bile by secreting HCO3 − into the bile duct lumen. This alkaline barrier may retain biliary bile salts in their polar, deprotonated, and membrane-impermeant state to avoid uncontrolled invasion of apolar toxic bile acids, which initiate apoptosis, autophagy and senescence. In primary biliary cholangitis, defects of the biliary HCO3 − umbrella, leading to impaired biliary HCO3 − secretion have been identified. Current medical therapies stabilize the putatively defective biliary HCO3 − umbrella and improve long-term prognosis.
AB - The biliary HCO3 − umbrella hypothesis states that human cholangiocytes and hepatocytes create a protective apical alkaline barrier against millimolar concentrations of potentially toxic glycine-conjugated bile salts in bile by secreting HCO3 − into the bile duct lumen. This alkaline barrier may retain biliary bile salts in their polar, deprotonated, and membrane-impermeant state to avoid uncontrolled invasion of apolar toxic bile acids, which initiate apoptosis, autophagy and senescence. In primary biliary cholangitis, defects of the biliary HCO3 − umbrella, leading to impaired biliary HCO3 − secretion have been identified. Current medical therapies stabilize the putatively defective biliary HCO3 − umbrella and improve long-term prognosis.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85047203223&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30259847
U2 - https://doi.org/10.1016/j.cld.2018.03.013
DO - https://doi.org/10.1016/j.cld.2018.03.013
M3 - Review article
C2 - 30259847
SN - 1089-3261
VL - 22
SP - 457
EP - 479
JO - Clinics in liver disease
JF - Clinics in liver disease
IS - 3
ER -