Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8258511 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2018 | 36 Pages |
Abstract
The nuclear receptor farnesoid X receptor (FXR) is the master regulator of bile acids (BAs) homeostasis since it transcriptionally drives modulation of BA synthesis, influx, efflux, and detoxification along the enterohepatic axis. Due to its crucial role, FXR alterations are involved in the progression of a plethora of BAs associated inflammatory disorders in the liver and in the gut. The involvement of the FXR pathway in cholestasis development and management has been elucidated so far with a direct role of FXR activating therapy in this condition. However, the recent identification of a new type of genetic progressive familial intrahepatic cholestasis (PFIC) linked to FXR mutations has strengthen also the bona fide beneficial effects of target therapies that by-pass FXR activation, directly promoting the action of its target, namely the enterokine FGF19, in the repression of hepatic BAs synthesis with reduction of total BA levels in the liver and serum, accomplishing one of the major goals in cholestasis. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni and Peter Jansen.
Keywords
ABCB4Retinoid X receptorPDGFCDCABSEPOCAABCB11BRICPFICFXRVDRUDCARXRNtcpNF-κBPXRTGR5FGFR4OATPBACSDrug-induced cholestasisLRH1TGF-βBcl-2 antagonist killer 1BAATFGF15/19OSTα/βHSCLBDDICICPDBDCTGFSHPIBDCYP7A1Mrp2FADDBcl2TNFαMDRfarnesoid X receptorHCCChenodeoxycholic acidobeticholic acidCholic acidBile acidsUrsodeoxycholic acidBak1Inflammatory bowel diseasetransforming growth factor-βtumor necrosis factor αFas-associated death domainDNA binding domainligand binding domainorganic solute transporterHepatic stellate cellssmall heterodimer partnerFibroblast growth factor 15/19Connective tissue growth factorplatelet-derived growth factornuclear factor-κBmultidrug resistance proteinOrganic anion transporting polypeptideBile salt export pumpHepatocellular carcinomacholestasisCholestasis of pregnancyBenign recurrent intrahepatic cholestasisProgressive familial intrahepatic cholestasisFarnesoid X receptor (FXR)fibroblast growth factor receptor 4Vitamin D receptorPregnane X receptorliver receptor homolog 1Nuclear receptornuclear receptors
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Authors
Marica Cariello, Elena Piccinin, Oihane Garcia-Irigoyen, Carlo Sabbà , Antonio Moschetta,