Title:Cell Death and microRNAs in Cholestatic Liver Diseases: Update on Potential Therapeutic Applications
Volume: 18
Issue: 8
Author(s): Rui Eduardo Castro*Cecília Maria Pereira Rodrigues
Affiliation:
- Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon,Portugal
Keywords:
Apoptosis, bile acids, cell death, cholestasis, microRNAs, necrosis, necroptosis, therapeutics.
Abstract: Cholestasis is the main pathogenic event in a wide range of genetic or acquired disorders of
bile acid synthesis or bile flow, resulting in intrahepatic and systemic accumulation of bile acids. In
turn, augmented levels of bile acids lead to hepatocellular injury and progressive liver damage, eventually
culminating in fibrosis and end-stage liver disease. In the injured cholestatic liver, apoptosis has
long been recognized as a direct consequence of bile acid-mediated injury. It is now apparent that inflammation
and necrosis play an equal or even more prevalent role. Ursodeoxycholic acid is the mainstream
treatment for several cholestatic syndromes, but has limited efficacy in certain circumstances.
With the notion that miRNAs play key roles in basic biological processes and that their deregulation is
common in human liver disease, prospective use of miRNAs as either therapeutic targets or disease
biomarkers is now being increasingly documented. Deciphering the exact contribution of each player
is crucial for directing efforts toward finding much needed novel therapeutic strategies for cholestasis.
