title: Syncoilin is an intermediate filament protein in activated hepatic stellate cells.
abstract: Hepatic stellate cells (HSCs) play an important role in several (patho)physiologic conditions in the liver. In response to chronic injury, HSCs are activated and change from quiescent to myofibroblast-like cells with contractile properties. This shift in phenotype is accompanied by a change in expression of intermediate filament (IF) proteins. HSCs express a broad, but variable spectrum of IF proteins. In muscle, syncoilin was identified as an alpha-dystrobrevin binding protein with sequence homology to IF proteins. We investigated the expression of syncoilin in mouse and human HSCs. Syncoilin expression in isolated and cultured HSCs was studied by qPCR, Western blotting, and fluorescence immunocytochemistry. Syncoilin expression was also evaluated in other primary liver cell types and in in vivo-activated HSCs as well as total liver samples from fibrotic mice and cirrhotic patients. Syncoilin mRNA was present in human and mouse HSCs and was highly expressed in in vitro- and in vivo-activated HSCs. Syncoilin protein was strongly upregulated during in vitro activation of HSCs and undetectable in hepatocytes and liver sinusoidal endothelial cells. Syncoilin mRNA levels were elevated in both CCl4- and common bile duct ligation-treated mice. Syncoilin immunocytochemistry revealed filamentous staining in activated mouse HSCs that partially colocalized with α-smooth muscle actin, β-actin, desmin, and α-tubulin. We show that in the liver, syncoilin is predominantly expressed by activated HSCs and displays very low-expression levels in other liver cell types, making it a good marker of activated HSCs. During in vitro activation of mouse HSCs, syncoilin is able to form filamentous structures or at least to closely interact with existing cellular filaments.
authors.affiliation: Liver Cell Biology Lab, Department of Cell Biology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium, elvrosse@vub.ac.be.
authors.forename: E
authors.initials: E
authors.lastname: Van Rossen
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Blijweert
authors.forename: N
authors.initials: N
authors.lastname: Eysackers
authors.forename: I
authors.initials: I
authors.lastname: Mannaerts
authors.forename: B
authors.initials: B
authors.lastname: Schroyen
authors.forename: A
authors.initials: A
authors.lastname: El Taghdouini
authors.forename: B
authors.initials: B
authors.lastname: Edwards
authors.forename: K E
authors.initials: KE
authors.lastname: Davies
authors.forename: E
authors.initials: E
authors.lastname: Sokal
authors.forename: M
authors.initials: M
authors.lastname: Najimi
authors.forename: H
authors.initials: H
authors.lastname: Reynaert
authors.forename: L A
authors.initials: LA
authors.lastname: van Grunsven
mesh_terms: D000199:Actins / Q000493:pharmacokinetics; D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D003893:Desmin / Q000494:pharmacology; D005355:Fibrosis / Q000473:pathology; D057809:HEK293 Cells; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000378:metabolism*; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000166:cytology / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism* / Q000493:pharmacokinetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D014404:Tubulin / Q000493:pharmacokinetics
chemical_list: D000199:Actins; D003893:Desmin; D007381:Intermediate Filament Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C503782:Sync protein, mouse; D014404:Tubulin; C544013:alpha-smooth muscle actin, mouse; D002251:Carbon Tetrachloride
references.citation: Hepatology. 2001 Jan;33(1):177-88
references.pmid: 11124834
references.citation: Int J Dev Biol. 1989 Mar;33(1):55-61
references.pmid: 2485702
references.citation: Hepatology. 1996 Jun;23(6):1538-45
references.pmid: 8675175
references.citation: Cell Mol Life Sci. 2008 Oct;65(19):2957-63
references.pmid: 18810324
references.citation: Biochem Biophys Res Commun. 2011 Mar 4;406(1):101-6
references.pmid: 21295548
references.citation: Bioessays. 2003 Mar;25(3):243-51
references.pmid: 12596228
references.citation: Trends Cardiovasc Med. 2002 Jul;12(5):224-8
references.pmid: 12161077
references.citation: Malar J. 2007 Dec 20;6:169
references.pmid: 18096071
references.citation: Mamm Genome. 2008 May;19(5):339-51
references.pmid: 18594912
references.citation: Hum Pathol. 2006 Sep;37(9):1200-10
references.pmid: 16938526
references.citation: Curr Opin Cell Biol. 2000 Feb;12(1):79-90
references.pmid: 10679360
references.citation: Hepatology. 2002 Feb;35(2):251-7
references.pmid: 11826396
references.citation: Int J Biochem Cell Biol. 2006 Feb;38(2):135-51
references.pmid: 16257564
references.citation: Annu Rev Biochem. 1994;63:345-82
references.pmid: 7979242
references.citation: Proteomics. 2010 Mar;10(5):1017-28
references.pmid: 20049859
references.citation: Proc Natl Acad Sci U S A. 2001 May 22;98(11):6156-61
references.pmid: 11353857
references.citation: Gut. 2002 Apr;50(4):571-81
references.pmid: 11889082
references.citation: J Clin Invest. 1992 Jul;90(1):282-7
references.pmid: 1634616
references.citation: Muscle Nerve. 2005 Dec;32(6):715-25
references.pmid: 16124004
references.citation: Histochem Cell Biol. 2009 Mar;131(3):313-25
references.pmid: 19052772
references.citation: Gastroenterology. 2008 May;134(6):1655-69
references.pmid: 18471545
references.citation: Cell Transplant. 2007;16(7):717-28
references.pmid: 18019361
references.citation: N Engl J Med. 2004 Nov 11;351(20):2087-100
references.pmid: 15537907
references.citation: J Cell Sci. 1994 Jun;107 ( Pt 6):1609-22
references.pmid: 7962201
references.citation: Physiol Rev. 2008 Jan;88(1):125-72
references.pmid: 18195085
references.citation: Gut. 2006 Sep;55(9):1276-89
references.pmid: 16484507
references.citation: Lab Invest. 2003 Feb;83(2):163-73
references.pmid: 12594232
references.citation: Cell. 1996 Aug 23;86(4):655-65
references.pmid: 8752219
references.citation: Nature. 1991 Oct 3;353(6343):445-8
references.pmid: 1832745
references.citation: Hepatology. 1984 Jul-Aug;4(4):709-14
references.pmid: 6204917
references.citation: J Biol Chem. 2002 Feb 1;277(5):3433-9
references.pmid: 11694502
references.citation: J Struct Biol. 2009 Mar;165(3):196-203
references.pmid: 19070665
references.citation: J Biol Chem. 2000 Jan 28;275(4):2247-50
references.pmid: 10644669
references.citation: Eur J Gastroenterol Hepatol. 2012 Dec;24(12):1370-80
references.pmid: 22895388
references.citation: Am J Physiol Cell Physiol. 2008 May;294(5):C1175-82
references.pmid: 18367591
references.citation: Histopathology. 1990 Jan;16(1):53-8
references.pmid: 2307416
references.citation: Histochem Cell Biol. 1999 Nov;112(5):387-401
references.pmid: 10603079
references.citation: Mol Biol Cell. 1999 Apr;10(4):1105-18
references.pmid: 10198060
references.citation: Neuromuscul Disord. 2007 Dec;17(11-12):970-9
references.pmid: 17629480
references.citation: J Microsc. 2006 Dec;224(Pt 3):213-32
references.pmid: 17210054
references.citation: Neuromuscul Disord. 2003 Jan;13(1):42-8
references.pmid: 12467731
references.citation: J Cell Sci. 2006 Oct 1;119(Pt 19):3981-93
references.pmid: 16988027
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9230-1
references.pmid: 22645354
references.citation: Hepatology. 2010 Feb;51(2):603-14
references.pmid: 19957378
references.citation: Lab Invest. 1996 Jan;74(1):265-78
references.pmid: 8569191
references.citation: J Biol Chem. 2001 Mar 2;276(9):6645-55
references.pmid: 11053421
references.citation: J Cell Sci. 2010 Aug 1;123(Pt 15):2543-52
references.pmid: 20587592
references.citation: J Hepatol. 2011 Dec;55(6):1353-60
references.pmid: 21803012
references.citation: Hepatology. 1999 Feb;29(2):520-7
references.pmid: 9918930
references.citation: Annu Rev Biochem. 1988;57:593-625
references.pmid: 3052284
references.citation: J Biol Chem. 1998 Apr 17;273(16):9797-803
references.pmid: 9545318
references.citation: Br J Pharmacol. 2010 Jan 1;159(2):304-15
references.pmid: 20039876
references.citation: J Hepatol. 2002 Feb;36(2):200-9
references.pmid: 11830331