IL-6-GP130 signaling protects human hepatocytes against lipid droplet accumulation in humanized liver models.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
14 04 2023
14 04 2023
Historique:
medline:
18
4
2023
entrez:
14
4
2023
pubmed:
15
4
2023
Statut:
ppublish
Résumé
Liver steatosis is an increasing health issue with few therapeutic options, partly because of a paucity of experimental models. In humanized liver rodent models, abnormal lipid accumulation in transplanted human hepatocytes occurs spontaneously. Here, we demonstrate that this abnormality is associated with compromised interleukin-6 (IL-6)-glycoprotein 130 (GP130) signaling in human hepatocytes because of incompatibility between host rodent IL-6 and human IL-6 receptor (IL-6R) on donor hepatocytes. Restoration of hepatic IL-6-GP130 signaling, through ectopic expression of rodent IL-6R, constitutive activation of GP130 in human hepatocytes, or humanization of an
Identifiants
pubmed: 37058568
doi: 10.1126/sciadv.adf4490
pmc: PMC10104468
doi:
Substances chimiques
Interleukin-6
0
Cytokine Receptor gp130
133483-10-0
Glycoproteins
0
Lipids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eadf4490Références
Semin Immunol. 2021 Apr;54:101509
pubmed: 34742624
J Hepatobiliary Pancreat Sci. 2011 Jan;18(1):13-22
pubmed: 20607568
J Mol Med (Berl). 1996 Sep;74(9):505-13
pubmed: 8892055
FASEB J. 2011 Dec;25(12):4301-11
pubmed: 21873555
Front Pharmacol. 2022 Jun 07;13:905936
pubmed: 35747747
Lab Invest. 2010 Aug;90(8):1169-78
pubmed: 20368703
Front Immunol. 2021 Jul 29;12:723544
pubmed: 34394131
J Hepatol. 2023 Jan;78(1):45-56
pubmed: 36049612
Gastroenterology. 2015 Sep;149(3):728-40.e15
pubmed: 26028580
Immunity. 2019 Apr 16;50(4):1007-1023
pubmed: 30995492
Endocrinology. 2011 Apr;152(4):1479-91
pubmed: 21303949
Eur J Biochem. 2001 Jan;268(1):160-7
pubmed: 11121117
Hepatogastroenterology. 2012 Jun;59(116):1208-12
pubmed: 22328286
J Hepatol. 2016 Jun;64(6):1403-15
pubmed: 26867490
Cell Mol Immunol. 2016 May;13(3):316-27
pubmed: 26908374
Methods Mol Biol. 2009;530:311-24
pubmed: 19266341
Sci Rep. 2022 Aug 18;12(1):14079
pubmed: 35982097
Gastroenterology. 2013 Dec;145(6):1209-14
pubmed: 24042096
Biochem Biophys Res Commun. 2011 Feb 18;405(3):405-10
pubmed: 21238430
Diabetes. 2010 Feb;59(2):347-57
pubmed: 19934001
Nat Biotechnol. 2007 Aug;25(8):903-10
pubmed: 17664939
Med. 2021 Jul 9;2(7):814-835
pubmed: 35291351
Hepatology. 2004 Oct;40(4):933-41
pubmed: 15382116
PLoS One. 2009 Nov 20;4(11):e7929
pubmed: 19936233
J Endocrinol. 2013 Aug 28;218(3):R25-36
pubmed: 23833274
Nat Rev Gastroenterol Hepatol. 2021 Nov;18(11):787-803
pubmed: 34211157
Nat Biotechnol. 2003 Jun;21(6):652-9
pubmed: 12730667
Adv Sci (Weinh). 2021 Oct;8(19):e2101188
pubmed: 34382351
EMBO J. 2000 Jun 1;19(11):2399-411
pubmed: 10835339
FEBS Lett. 1997 Jan 13;401(1):49-52
pubmed: 9003804
J Hepatol. 2022 Apr;76(4):934-945
pubmed: 34793866
Nature. 2009 Jan 8;457(7226):200-4
pubmed: 19020503
World J Gastroenterol. 2006 Dec 14;12(46):7413-20
pubmed: 17167827
World J Gastroenterol. 2012 Feb 28;18(8):727-35
pubmed: 22371632
Front Immunol. 2019 May 29;10:1165
pubmed: 31191538
J Leukoc Biol. 1993 Feb;53(2):126-32
pubmed: 8445325
Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Mar;1864(3):271-280
pubmed: 30553055
PLoS One. 2014 Apr 24;9(4):e96053
pubmed: 24763697
Biochim Biophys Acta. 2015 May;1852(5):1001-11
pubmed: 25660446
FASEB J. 2021 Feb;35(2):e21286
pubmed: 33484478
Dig Liver Dis. 2009 Nov;41(11):823-8
pubmed: 19403348
J Immunol. 1994 Aug 15;153(4):1744-53
pubmed: 7519211
Semin Liver Dis. 2020 May;40(2):189-212
pubmed: 32074631