title: Loss of α1,6-fucosyltransferase suppressed liver regeneration: implication of core fucose in the regulation of growth factor receptor-mediated cellular signaling.
abstract: Core fucosylation is an important post-translational modification, which is catalyzed by α1,6-fucosyltransferase (Fut8). Increased expression of Fut8 has been shown in diverse carcinomas including hepatocarcinoma. In this study, we investigated the role of Fut8 expression in liver regeneration by using the 70% partial hepatectomy (PH) model, and found that Fut8 is also critical for the regeneration of liver. Interestingly, we show that the Fut8 activities were significantly increased in the beginning of PH (~4d), but returned to the basal level in the late stage of PH. Lacking Fut8 led to delayed liver recovery in mice. This retardation mainly resulted from suppressed hepatocyte proliferation, as supported not only by a decreased phosphorylation level of epidermal growth factor (EGF) receptor and hepatocyte growth factor (HGF) receptor in the liver of Fut8(-/-) mice in vivo, but by the reduced response to exogenous EGF and HGF of the primary hepatocytes isolated from the Fut8(-/-) mice. Furthermore, an administration of L-fucose, which can increase GDP-fucose synthesis through a salvage pathway, significantly rescued the delayed liver regeneration of Fut8(+/-) mice. Overall, our study provides the first direct evidence for the involvement of Fut8 in liver regeneration.
authors: Division of Regulatory Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.
authors: Yuqin
authors: Y
authors: Wang
authors: Division of Regulatory Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.
authors: Tomohiko
authors: T
authors: Fukuda
authors: Division of Regulatory Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.
authors: Tomoya
authors: T
authors: Isaji
authors: Division of Regulatory Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.
authors: Jishun
authors: J
authors: Lu
authors: Division of Regulatory Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.
authors: Wei
authors: W
authors: Gu
authors: Division of Regulatory Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.
authors: Ho-Hsun
authors: HH
authors: Lee
authors: Department of Radiopharmacy, Tohoku Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.
authors: Yasuhito
authors: Y
authors: Ohkubo
authors: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan.
authors: Yoshihiro
authors: Y
authors: Kamada
authors: Disease Glycomics Team, RIKEN, Wako, Saitama, 351-0198, Japan.
authors: Naoyuki
authors: N
authors: Taniguchi
authors: Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan.
authors: Eiji
authors: E
authors: Miyoshi
authors: Division of Regulatory Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi, 981-8558, Japan.
authors: Jianguo
authors: J
authors: Gu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005643:Fucose / Q000008:administration & dosage / Q000378:metabolism; D005647:Fucosyltransferases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005838:Genotype; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008115:Liver Regeneration / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D017978:Receptors, Growth Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D017978:Receptors, Growth Factor; D005643:Fucose; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase
references: Int J Cancer. 2000 Dec 15;88(6):914-9
references: 11093814
references: Nat Commun. 2014;5:3862
references: 24844558
references: J Biol Chem. 2003 Jan 31;278(5):3466-73
references: 12427744
references: Blood. 2003 Mar 1;101(5):1705-12
references: 12406889
references: Glycobiology. 2003 Jul;13(7):41R-53R
references: 12651883
references: Cancer Res. 2003 Nov 15;63(22):7753-9
references: 14633700
references: J Mol Biol. 2004 Mar 5;336(5):1239-49
references: 15037082
references: Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4477-82
references: 15070743
references: Annu Rev Biochem. 2004;73:491-537
references: 15189151
references: Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10608-13
references: 15249655
references: Nat Rev Mol Cell Biol. 2004 Oct;5(10):836-47
references: 15459664
references: J Clin Invest. 1988 Aug;82(2):450-9
references: 3042806
references: Hepatology. 1991 Apr;13(4):683-8
references: 1849114
references: J Biol Chem. 1996 Nov 1;271(44):27810-7
references: 8910378
references: Adv Biochem Eng Biotechnol. 2005;93:101-34
references: 15791946
references: Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15791-6
references: 16236725
references: J Biol Chem. 2006 Feb 3;281(5):2572-7
references: 16316986
references: Hepatology. 2006 Feb;43(2 Suppl 1):S45-53
references: 16447274
references: J Biol Chem. 2006 Dec 15;281(50):38343-50
references: 17043354
references: Hepatology. 2007 Jun;45(6):1471-7
references: 17427161
references: J Cell Physiol. 2007 Nov;213(2):286-300
references: 17559071
references: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17081-6
references: 17940036
references: Int J Cancer. 2008 Aug 1;123(3):641-6
references: 18491404
references: Nat Protoc. 2008;3(7):1167-70
references: 18600221
references: Dev Cell. 2010 Feb 16;18(2):175-89
references: 20159590
references: J Biol Chem. 2010 Jun 4;285(23):17301-9
references: 20335177
references: EMBO Mol Med. 2010 Aug;2(8):294-305
references: 20652897
references: J Biol Chem. 2011 May 27;286(21):18434-43
references: 21471224
references: Curr Opin Cell Biol. 2011 Aug;23(4):383-92
references: 21616652
references: Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12669-74
references: 21768335
references: Genes Cells. 2011 Nov;16(11):1071-80
references: 22023369
references: Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):630-5
references: 23267084
references: Hepatology. 2013 May;57(5):1992-2003
references: 23299899
references: FASEB J. 2013 Oct;27(10):3947-58
references: 23796784
references: Nat Rev Mol Cell Biol. 2014 Mar;15(3):163-77
references: 24556839
references: World J Gastroenterol. 2014 Aug 21;20(31):10691-702
references: 25152573
references: Expert Rev Gastroenterol Hepatol. 2014 Nov;8(8):897-907
references: 24964729
references: J Hepatol. 2002 Jun;36(6):725-33
references: 12044521