1 40 1 Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. URL Address <a href="http://doi.org/10.1002/hep.22627" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/hep.22627</a> Pages 297–305 Issue 1 Volume 49 Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene expression. Publisher An entity responsible for making the resource available Hepatology (Baltimore, Md.) Date A point or period of time associated with an event in the lifecycle of the resource 2009 2009-01 Subject The topic of the resource Butadienes/pharmacology; Carcinoma; Cell Line; Chenodeoxycholic Acid/*pharmacology; Cholesterol 7-alpha-Hydroxylase/*biosynthesis; Cytoplasmic and Nuclear/metabolism/physiology; DNA-Binding Proteins/metabolism; Fibroblast Growth Factor; Fibroblast Growth Factors/drug effects/*physiology; Gene Expression/drug effects; Hepatocellular/metabolism; Hepatocytes/metabolism; Humans; Isoxazoles/pharmacology; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3/metabolism; Nitriles/pharmacology; Receptor; Receptors; Signal Transduction/drug effects; Transcription Factors/metabolism; Tumor; Type 4/antagonists & inhibitors Creator An entity primarily responsible for making the resource Song Kwang-Hoon; Li Tiangang; Owsley Erika; Strom Stephen; Chiang John Y L Description An account of the resource UNLABELLED: Mouse fibroblast growth factor 15 (FGF15) and human ortholog FGF19 have been identified as the bile acid-induced intestinal factors that mediate bile acid feedback inhibition of cholesterol 7alpha-hydroxylase gene (C YP7A1) transcription in mouse liver. The mechanism underlying FGF15/FGF19 inhibition of bile acid synthesis in hepatocytes remains unclear. Chenodeoxycholic acid (CDCA) and the farnesoid X receptor (FXR)-specific agonist GW4064 strongly induced FGF19 but inhibited CYP7A1 messenger RNA (mRNA) levels in primary human hepatocytes. FGF19 strongly and rapidly repressed CYP7A1 but not small heterodimer partner (SHP) mRNA levels. Kinase inhibition and phosphorylation assays revealed that the mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (MAPK/Erk1/2) pathway played a major role in mediating FGF19 inhibition of CYP7A1. However, small interfering RNA (siRNA) knockdown of SHP did not affect FGF19 inhibition of CYP7A1. Interestingly, CDCA stimulated tyrosine phosphorylation of the FGF receptor 4 (FGFR4) in hepatocytes. FGF19 antibody and siRNA specific to FGFR4 abrogated GW4064 inhibition of CYP7A1. These results suggest that bile acid-activated FXR is able to induce FGF19 in hepatocytes to inhibit CYP7A1 by an autocrine/paracrine mechanism. CONCLUSION: The hepatic FGF19/FGFR4/Erk1/2 pathway may inhibit CYP7A1 independent of SHP. In addition to inducing FGF19 in the intestine, bile acids in hepatocytes may activate the liver FGF19/FGFR4 signaling pathway to inhibit bile acid synthesis and prevent accumulation of toxic bile acid in human livers. Identifier An unambiguous reference to the resource within a given context <a href="http://doi.org/10.1002/hep.22627" target="_blank" rel="noreferrer noopener">10.1002/hep.22627</a> Rights Information about rights held in and over the resource Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s). 2009 Butadienes/pharmacology Carcinoma Cell Line Chenodeoxycholic Acid/*pharmacology Chiang John Y L Cholesterol 7-alpha-Hydroxylase/*biosynthesis Cytoplasmic and Nuclear/metabolism/physiology Department of Integrative Medical Sciences DNA-Binding Proteins/metabolism Fibroblast Growth Factor Fibroblast Growth Factors/drug effects/*physiology Gene Expression/drug effects Hepatocellular/metabolism Hepatocytes/metabolism Hepatology (Baltimore, Md.) Humans Isoxazoles/pharmacology Li Tiangang Mitogen-Activated Protein Kinase 1/metabolism Mitogen-Activated Protein Kinase 3/metabolism NEOMED College of Medicine Nitriles/pharmacology Owsley Erika Receptor Receptors Signal Transduction/drug effects Song Kwang-Hoon Strom Stephen Transcription Factors/metabolism Tumor Type 4/antagonists & inhibitors