Identification of a novel FGF, FGF-21, preferentially expressed in the liver

Nishimura, Tetsuya; Nakatake, Yuhki; Konishi, Morichika; Itoh, Nobuyuki

doi:10.1016/s0167-4781(00)00067-1

Cited by 727 publications

(544 citation statements)

References 20 publications

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“…Transgenic animals with FGF19 targeted to muscle exhibit an increased metabolic rate and decreased adiposity accompanied by a reduction in expression of liver acetyl CoA carboxylase 2 and triglyceride levels 36 and liver abnormalities associated with cancer in aging mice. 37 FGF21 appears to be specifically expressed in the liver 38 hepatocyte-specific FGFR4 functions and nonparenchymal cells of liver expressing other FGFR isotypes is under investigation.…”

Section: Discussionmentioning

confidence: 99%

Role of Fibroblast Growth Factor Type 1 and 2 in Carbon Tetrachloride-Induced Hepatic Injury and Fibrogenesis

Wang

Jin

et al. 2003

The American Journal of Pathology

150

126

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Genomic ablation of hepatocyte-specific fibroblast growth factor receptor (FGFR)4 in mice revealed a role of FGF signaling in cholesterol and bile acid metabolism and hepatolobular restoration in response to injury without effect on liver development or hepatocyte proliferation. Although the potential role of all 23 FGF polypeptides in the liver is still unclear, the most widely studied prototypes, FGF1 and FGF2, are present and have been implicated in liver cell growth and function in vitro. To determine whether FGF1 and FGF2 play a role in response to injury and fibrosis, we examined the impact of both acute and chronic exposure to carbon tetrachloride (CCl 4 ) in the livers of FGF1-and FGF2-deficient mice. After acute CCl 4 exposure, FGF1(؊/؊)FGF2(؊/؊) mice exhibited an accelerated release of serum alanine aminotransferase similar to FGFR4 deficiency, but no effect on overall hepatolobular restoration or bile acid metabolism. The fibroblast growth factors (FGFs) comprise a family of 23 reported members that have varying affinities for variants of four different FGF receptor kinases (FGFR1 to FGFR4). 1-3 FGF1 and FGF2, the first two cloned members of the FGF family, 4,5 have received the most study, are widely expressed, and thus, predicted to be involved in tissue-specific functions and associated pathologies at their site of expression. 6,7 In vitro FGF1 affects cells of multiple origin whereas activity of FGF2 appears more limited to cells derived from mesenchyme and neuroectoderm. 8 FGF1 and FGF2 have been implicated in derivation of the liver from foregut endoderm. 9 However, mice lacking FGF1, FGF2, or both FGF1 and FGF2 are viable, fertile, and grossly indistinguishable from wild type (WT) except for modest defects in cardiovascular tissue, healing of skin wounds, and neuronal tissue. 3,10,11 This suggests that FGF1 and FGF2 alone are not essential for embryonic development or are compensated by other members of the extensive FGF ligand family. Consequently, FGF1-and FGF2-deficient animals are available for study of the role of the two factors in adult tissue homeostasis. Despite their ubiquity, little has emerged except for the modest effects of ablation of FGF1 and FGF2 in the cardiovascular, skin, and nervous systems.Although the levels of mRNA transcripts are low, longlived FGF1 and FGF2 polypeptides are present in the resting liver at significant levels. 12 This suggests that a significant reservoir of both ligands is present in the resting liver in an inactive state before activation and

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Section: Discussionmentioning

confidence: 99%

Role of Fibroblast Growth Factor Type 1 and 2 in Carbon Tetrachloride-Induced Hepatic Injury and Fibrogenesis

Wang

Jin

et al. 2003

The American Journal of Pathology

150

126

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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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“…Fibroblast growth factor 21 (FGF21) was first identified in the liver [Nishimura et al, 2000] [Murphy et al, 2013]. These effects were 77 more pronounced in hamsters in the summer long-day (LD) state when the hamsters maintain a high 78 body weight than in hamsters exposed to short days (SD) that promotes the winter-adaptive state.…”

Section: Introduction 44mentioning

confidence: 99%