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Expression of hepatic Fibroblast Growth Factor 19 is enhanced in Primary Biliary Cirrhosis and correlates with severity of the disease.

Wunsch E, Milkiewicz M, Wasik U, Trottier J, Kempińska-Podhorodecka A, Elias E, Barbier O, Milkiewicz P - Sci Rep (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, Szczecin, Poland.

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.

No MeSH data available.


Related in: MedlinePlus

Correlation between serum FGF19 (pg/ml), laboratory parameters and Mayo Risk Score.FGF19 serum concentration correlated with several laboratory parameters: (A) hemoglobin, (B) albumin, (C) AST and (D) total bilirubin. No correlation between serum FGF19 levels and (E) ALP was seen. (F) There was significant relationship between FGF19 concentrations and Mayo Risk Score.
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f1: Correlation between serum FGF19 (pg/ml), laboratory parameters and Mayo Risk Score.FGF19 serum concentration correlated with several laboratory parameters: (A) hemoglobin, (B) albumin, (C) AST and (D) total bilirubin. No correlation between serum FGF19 levels and (E) ALP was seen. (F) There was significant relationship between FGF19 concentrations and Mayo Risk Score.

Mentions: Serum levels of FGF19 were unrelated to age, gender and presence of cirrhosis (data not shown). The univariate analysis showed the significant correlation between the serum FGF19 and several laboratory parameters such as: hemoglobin (r = −0.394, p = 0.01), albumin (r = −0.408, p = 0.007), total bilirubin (r = 0.577, p < 0.0001) and AST (r = 0.328, p = 0.03). In the multivariate analysis, total bilirubin and hemoglobin were independent variables (p < 0.0001). There was a significant relationship between FGF19 concentrations and Mayo Risk Score for PBC (r = 0.514, p = 0.0004). These data are shown in Fig. 1. FGF19 correlated with total bile acid concentration and glycine and taurine conjugates of cholic acid (CA), chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA). It also correlated with 3-O-glucuronide conjugates of CDCA and lithocholic acid (LCA) (Table 1). In the multivariate analysis, glycine species of CDCA, glycine and taurine conjugate of UDCA and finally 3-O-glucuronide of LCA were independent variables related to serum FGF-19 levels (p < 0.0001).


Expression of hepatic Fibroblast Growth Factor 19 is enhanced in Primary Biliary Cirrhosis and correlates with severity of the disease.

Wunsch E, Milkiewicz M, Wasik U, Trottier J, Kempińska-Podhorodecka A, Elias E, Barbier O, Milkiewicz P - Sci Rep (2015)

Correlation between serum FGF19 (pg/ml), laboratory parameters and Mayo Risk Score.FGF19 serum concentration correlated with several laboratory parameters: (A) hemoglobin, (B) albumin, (C) AST and (D) total bilirubin. No correlation between serum FGF19 levels and (E) ALP was seen. (F) There was significant relationship between FGF19 concentrations and Mayo Risk Score.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4544021&req=5

f1: Correlation between serum FGF19 (pg/ml), laboratory parameters and Mayo Risk Score.FGF19 serum concentration correlated with several laboratory parameters: (A) hemoglobin, (B) albumin, (C) AST and (D) total bilirubin. No correlation between serum FGF19 levels and (E) ALP was seen. (F) There was significant relationship between FGF19 concentrations and Mayo Risk Score.
Mentions: Serum levels of FGF19 were unrelated to age, gender and presence of cirrhosis (data not shown). The univariate analysis showed the significant correlation between the serum FGF19 and several laboratory parameters such as: hemoglobin (r = −0.394, p = 0.01), albumin (r = −0.408, p = 0.007), total bilirubin (r = 0.577, p < 0.0001) and AST (r = 0.328, p = 0.03). In the multivariate analysis, total bilirubin and hemoglobin were independent variables (p < 0.0001). There was a significant relationship between FGF19 concentrations and Mayo Risk Score for PBC (r = 0.514, p = 0.0004). These data are shown in Fig. 1. FGF19 correlated with total bile acid concentration and glycine and taurine conjugates of cholic acid (CA), chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA). It also correlated with 3-O-glucuronide conjugates of CDCA and lithocholic acid (LCA) (Table 1). In the multivariate analysis, glycine species of CDCA, glycine and taurine conjugate of UDCA and finally 3-O-glucuronide of LCA were independent variables related to serum FGF-19 levels (p < 0.0001).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, Szczecin, Poland.

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.

No MeSH data available.


Related in: MedlinePlus