Article Text

other Versions

PDF
Targeting TGR5 in cholangiocyte proliferation: default topic
  1. Cecília M P Rodrigues1,
  2. Han Moshage2
  1. 1Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), University of Lisbon, Lisbon, Portugal
  2. 2Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  1. Correspondence to Professor Cecília M P Rodrigues, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, Lisbon 1649-003, Portugal; cmprodrigues{at}ff.ulisboa.pt

Statistics from Altmetric.com

The transmembrane G protein-coupled receptor TGR5 binds to and is activated by bile acids.1 ,2 TGR5 is widely distributed, in animals and humans, in the gallbladder, liver, brown adipose tissue, muscle, intestine, kidney, placenta and brain. In the liver, TGR5 appears in sinusoidal endothelial cells, bile duct epithelial cells and Kupffer cells. Interestingly, the ubiquitous TGR5 expression positions previously unsuspected tissues such as muscle, brain and adipose tissue, and cells such as macrophages and endothelial cells, as potential targets of bile acid signalling. Bile acid binding to TGR5 activates multiple signalling routes involved in a multitude of processes thus potentially affecting metabolism, inflammation, fibrosis and carcinogenesis. Lithocholic acid is the strongest natural ligand of TGR5,1 ,2 while INT-777 is a semisynthetic TGR5 agonist.3 Further development of semisynthetic bile acid analogues that target TGR5 or intracellular nuclear receptors, such as the Farnesoid X receptor (FXR), holds great expectations to treat chronic liver disease, hepatocellular cancer and extrahepatic inflammatory and metabolic diseases. Randomised, placebo controlled clinical trials for the treatment of non-alcoholic steatohepatitis and primary biliary cirrhosis with FXR agonist obeticholic acid are the first initiated trials.

Cholangiocarcinoma (CCA) is the second most common primary liver tumour and accounts for ∼3% of all …

View Full Text

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles