title: Expression of hepatic Fibroblast Growth Factor 19 is enhanced in Primary Biliary Cirrhosis and correlates with severity of the disease.
abstract: Cholestasis induces adaptive mechanisms protecting the liver against bile acids (BA) toxicity including modulation of BA synthesis. Whether fibroblast growth factor 19 (FGF19) or farnesoid X receptor (FXR) dependent signaling are involved in the regulation of BA homeostasis in primary biliary cirrhosis (PBC) remains unknown. Here we analyzed hepatic expression of FGF19 and other genes relevant to the adaptive response to cholestasis in tissues from non-cirrhotic (n = 24) and cirrhotic (n = 21) patients along with control tissues (n = 21). Moreover we searched for relationships between serum FGF19 and laboratory/clinical findings in 51 patients. Hepatic FGF19 mRNA expression was increased in non-cirrhotic and cirrhotic tissues (9-fold,p = 0.01; 69-fold,p < 0.0001, respectively). Protein levels of FGF19, FGF receptor 4, FXR and short heterodimer partner were increased in cirrhotic livers (9-fold, p < 0.001; 3.5-fold,p = 0.007; 2.4-fold,p < 0.0001; 2.8-fold,p < 0.0001 vs controls, respectively) which was accompanied by down-regulation of CYP7A1 (50% reduction, p = 0.006). Serum and liver levels of FGF19 correlated with worse liver biochemistry, BAs, quality of life and Mayo Risk Score. Serum FGF19 was elevated in UDCA non-responders. We conclude that PBC induces characteristic changes in liver expression of BAs synthesis regulatory molecules. FGF19 correlates with severity of liver disease and can potentially serve as an indicator of chronic cholestatic liver injury.
authors: Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, Szczecin, Poland.
authors: Ewa
authors: E
authors: Wunsch
authors: Department of Medical Biology, Pomeranian Medical University in Szczecin, Szczecin, Poland.
authors: Małgorzata
authors: M
authors: Milkiewicz
authors: Department of Medical Biology, Pomeranian Medical University in Szczecin, Szczecin, Poland.
authors: Urszula
authors: U
authors: Wasik
authors: Laboratory of Molecular Pharmacology, CHU-de-Québec &Faculty of Pharmacy, Laval University, Québec, QC, Canada.
authors: Jocelyn
authors: J
authors: Trottier
authors: Department of Medical Biology, Pomeranian Medical University in Szczecin, Szczecin, Poland.
authors: Agnieszka
authors: A
authors: Kempińska-Podhorodecka
authors: University of Birmingham, Birmingham, United Kingdom.
authors: Elwyn
authors: E
authors: Elias
authors: Laboratory of Molecular Pharmacology, CHU-de-Québec &Faculty of Pharmacy, Laval University, Québec, QC, Canada.
authors: Olivier
authors: O
authors: Barbier
authors: Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, Szczecin, Poland.|Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery of the Medical University of Warsaw, Warsaw, Poland.
authors: Piotr
authors: P
authors: Milkiewicz
mesh_terms: D001647:Bile Acids and Salts / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011788:Quality of Life; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D001647:Bile Acids and Salts; C117476:FGF19 protein, human; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4