Structure and expression of a novel human FGF, FGF-19, expressed in the fetal brain

Nishimura, Tetsuya; Utsunomiya, Yukari; Hoshikawa, Masamitsu; Ohuchi, Hideyo; Itoh, Nobuyuki

doi:10.1016/s0167-4781(98)00255-3

Cited by 210 publications

(141 citation statements)

References 18 publications

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“…FGF19 is not expressed in normal liver. 7,12 However, we found high levels of FGF19 mRNA in liver of patients with extrahepatic cholestasis (Fig. 1).…”

Section: Discussionmentioning

confidence: 69%

“…FGF19 mRNA was not detected in seven of 10 control liver specimens, in line with the reported absence of FGF19 in normal adult liver. 7,12 Average expression of FGF19 mRNA was 31-fold and 374-fold higher in the cholestatic group in comparison with drained (P Ͻ 0.001) and control groups (P Ͻ 0.001), respectively ( Table 2). Although FGF19 mRNA was readily detected in liver biopsy specimens of all drained patients, the expression level appeared biologically trivial because plasma FGF19 levels in the drained group were similar to control levels.…”

Section: Fgf19 Mrna Is Expressed In Liver Of Patients With Extrahepatmentioning

confidence: 99%

“…Combined with absent expression of FGF19 in normal human liver, plasma FGF19 is thus expected to be lowered in patients with extrahepatic cholestasis. 6,7,12 In the current study, we sought to determine plasma FGF19 levels in patients with extrahepatic cholestasis, to address the role of FGF19 in regulation of CYP7A1 expression under conditions of extrahepatic cholestasis, and to study adaptive changes in the liver under conditions of extrahepatic cholestasis.…”

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confidence: 99%

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High expression of the bile salt-homeostatic hormone fibroblast growth factor 19 in the liver of patients with extrahepatic cholestasis #

Schaap¹,

et al. 2009

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Fibroblast growth factor 19 (FGF19) is an endocrine factor produced by the small intestine in response to uptake of luminal bile salts. In the liver, FGF19 binds to FGF receptor-4, resulting in down-regulation of cytochrome P (CYP) 7A1 and reduced bile salt synthesis. Down-regulation of CYP7A1 under cholestatic conditions has been attributed to bile salt-mediated induction of the transcriptional repressor short heterodimer partner (SHP), because the interrupted enterohepatic cycle of bile salts is thought to abrogate intestinal FGF19 production and thus result in lowering of plasma FGF19 levels. Unexpectedly, we observed marked elevation of plasma FGF19 in patients with extrahepatic cholestasis caused by a pancreatic tumor (2.3 ؎ 2.3 in cholestatic versus 0.40 ؎ 0.25 ng/mL and 0.29 ؎ 0.12 ng/mL in postcholestatic patients who received preoperative drainage by biliary stenting, P ‫؍‬ 0.004, and noncholestatic control patients, P ‫؍‬ 0.04, respectively). Although FGF19 messenger RNA (mRNA) is virtually absent in normal liver, FGF19 mRNA was strongly increased (31-fold to 374-fold, P < 0.001) in the liver of cholestatic patients in comparison with drained and control patients. In the absence of changes in SHP mRNA, CYP7A1 mRNA was strongly reduced (7.2-fold to 24-fold, P < 0. B ecause they are potent detergents, synthesis of bile salts is subject to rigorous regulation. 1,2 The principal target for control of bile salt synthesis is the cytochrome P (CYP) 7A1 gene, which encodes the ratedetermining enzyme in the dominant biosynthetic pathway. Regulation of CYP7A1 occurs primarily at the transcriptional level and involves several nuclear hormone receptors. Among these ligand-activated transcription factors, the bile salt receptor FXR (farnesoid-X receptor) plays a key role in bile salt-mediated repression of CYP7A1. 2-4 Activation of hepatic FXR induces expression of short heterodimer partner (SHP), a transcriptional repressor that diminishes the transactivation potential of several transcription factors required for efficient CYP7A1 expression. [3][4][5] Activation of intestinal FXR by reabsorbed bile salts induces expression and portal release of FGF19 (fibroblast growth factor 19, termed Fgf15 in rodents). 6,7 Binding of FGF19/ Fgf15 to the cell surface receptor FGFR4 results in activation of mitogen-activated protein kinase pathways and downregulation of CYP7A1. 7,8 Studies in mice with intestine-specific or liver-specific disruption of the Fxr gene revealed that administration of a synthetic FXR agonist failed to repress Cyp7a1 in animals deficient in intestinal Fxr. 9 This study thus implied an important role for intestinal Fgf15 in regulation of bile salt synthesis.

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“…FGF19 is not expressed in normal liver. 7,12 However, we found high levels of FGF19 mRNA in liver of patients with extrahepatic cholestasis (Fig. 1).…”

Section: Discussionmentioning

confidence: 69%

Section: Fgf19 Mrna Is Expressed In Liver Of Patients With Extrahepatmentioning

confidence: 99%

mentioning

confidence: 99%

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High expression of the bile salt-homeostatic hormone fibroblast growth factor 19 in the liver of patients with extrahepatic cholestasis #

Schaap¹,

et al. 2009

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“…Production of the control b-actin products was observed throughout the lanes with mRNAs, N indicates no RNA samples; P indicates mRNA from L361-M3E cells as a template Oncogene Hst-1/Fgf-4 expression in the adult mice H Yamamoto et al Purkinje cells in adult and developing CNS in human and rats (Todo et al, 1998;Nakamura et al, 1999). FGF-19, a novel member of the human FGF family, was expressed in fetal brain (Nishimura et al, 1999). In the chick system, a model for FGF function in speci®cation and patterning of the midbrain was proposed (Shamin et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Detection of spatial localization of Hst-1/Fgf-4 gene expression in brain and testis from adult mice

Yamamoto¹,

Ochiya²,

Takahama

et al. 2000

Oncogene

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“…FGFs 1-9 range in size from ϳ150 to 260 amino acid residues and have a conserved ϳ120-amino acid residue core with ϳ30 to 70% sequence identity (Ornitz and Itoh, 2001;Itoh and Ornitz, 2004). Based on their conserved amino acid sequences, Fgfs 10 -14 and 16 -23 were isolated by conducting a homology-based polymerase chain reaction or identified by homology-based searches in nucleotide sequence databases (Yamasaki et al, 1996;Smallwood et al, 1996;Miyake et al, 1998;Hoshikawa et al, 1998;Nishimura et al, 1999Nishimura et al, , 2000Ohmachi et al, 2000;Nakatake et al, 2001;Yamashita et al, 2000). In addition, Fgf15 was identified as a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx (McWhirter et al, 1997).…”

Section: Identification Of the Mouse Fgf Gene Familymentioning

confidence: 99%

Functional evolutionary history of the mouse Fgf gene family

Itoh

Ornitz

2007

Developmental Dynamics

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Structure and expression of a novel human FGF, FGF-19, expressed in the fetal brain

Cited by 210 publications

References 18 publications

High expression of the bile salt-homeostatic hormone fibroblast growth factor 19 in the liver of patients with extrahepatic cholestasis #

High expression of the bile salt-homeostatic hormone fibroblast growth factor 19 in the liver of patients with extrahepatic cholestasis #

Detection of spatial localization of Hst-1/Fgf-4 gene expression in brain and testis from adult mice

Functional evolutionary history of the mouse Fgf gene family

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