2010
DOI: 10.1074/jbc.m109.068783
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FGF19-induced Hepatocyte Proliferation Is Mediated through FGFR4 Activation

Abstract: FGF19 and FGF21, unique members of the fibroblast growth factor (FGF) family, are hormones that regulate glucose, lipid, and energy homeostasis. Increased hepatocyte proliferation and liver tumor formation have also been observed in FGF19 transgenic mice. Here, we report that, in contrast to FGF19, FGF21 does not induce hepatocyte proliferation in vivo. To identify the mechanism for FGF19-induced hepatocyte proliferation, we explored similarities and differences in receptor specificity between FGF19 and FGF21.… Show more

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Cited by 161 publications
(213 citation statements)
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“…Unlike other FGF molecules, FGF21 does not possess the mitogenic activity (3,4) and acts as an important metabolic regulator (3). The metabolic activity of FGF21 was first discovered in a cellbased high throughput screening as a positive hit for its ability to induce glucose uptake in adipocytes (3).…”
mentioning
confidence: 99%
“…Unlike other FGF molecules, FGF21 does not possess the mitogenic activity (3,4) and acts as an important metabolic regulator (3). The metabolic activity of FGF21 was first discovered in a cellbased high throughput screening as a positive hit for its ability to induce glucose uptake in adipocytes (3).…”
mentioning
confidence: 99%
“…1,3,4 Recent studies have demonstrated that FGF19 plays key roles in hepatocarcinogenesis. 5 Genetic aberrations in FGF21 have not been reported in liver cancer genomics studies. Up-regulation of FGF21 in transgenic mouse models delayed or hampered HCC proliferation.…”
Section: Replymentioning
confidence: 99%
“…5 To further evaluate the prognostic significance of FIB-4 in hepatitis B-associated HCC, herein we involved 324 hepatitis B surface antigen-positive HCC patients. After a median follow-up period of 44 months, 204 Fig.…”
Section: Fib-4 As a Prognostic Model For Patients With Hepatitis B-asmentioning
confidence: 99%
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“…A key regulator of the FGFR4 pathway is its coreceptor klotho-beta (KLB), a 130 kDa transmembrane protein that exhibits a more restricted expression profile in adipose, liver and pancreas tissues. KLB and FGFR4 are both expressed at high levels in mature hepatocytes, where KLB stabilizes FGF19-FGFR4 binding to regulate production of cholesterol 7a-hydroxylase (CYP7A1) and hepatocyte proliferation (Kurosu et al, 2007;Lin et al, 2007;Wu et al, 2010). It has also been identified that FGFR4 is part of a complex with MT1-MMP, where MT1-MMP and FGFR4 are regulated in an opposite direction depending on the tumor progression and the presence of FGFR4 SNP Gly388Arg (Hotary et al, 2000;Lehti et al, 2000;Okada et al, 1995;Sugiyama et al, 2010).…”
Section: Functionmentioning
confidence: 99%