title: Cell Death and microRNAs in Cholestatic Liver Diseases: Update on Potential Therapeutic Applications.
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.
authors.affiliation: Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Rui Eduardo
authors.initials: RE
authors.lastname: Castro
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Cecília Maria Pereira
authors.initials: CMP
authors.lastname: Rodrigues
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000494:pharmacology / Q000627:therapeutic use; D002780:Cholestasis, Intrahepatic / Q000188:drug therapy / Q000235:genetics*; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000187:drug effects; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002756:Cholagogues and Choleretics; D005819:Genetic Markers; D035683:MicroRNAs; D014580:Ursodeoxycholic Acid
keywords: Apoptosis; bile acids; cell death; cholestasis; microRNAs; necroptosis; necrosis; therapeutics