title: Sublytic C5b-9 triggers glomerular mesangial cell apoptosis via XAF1 gene activation mediated by p300-dependent IRF-1 acetylation.
abstract: The apoptosis of glomerular mesangial cells (GMCs) in rat Thy-1 nephritis (Thy-1N), a model of human mesangioproliferative glomerulonephritis (MsPGN), is accompanied by sublytic C5b-9 deposition. However, the mechanism by which sublytic C5b-9 induces GMC apoptosis is unclear. In the present studies, the effect of X-linked inhibitor of apoptosis-associated factor 1 (XAF1) expression on GMC apoptosis and the role of p300 and interferon regulatory factor-1 (IRF-1) in mediating XAF1 gene activation were determined, both in the GMCs induced by sublytic C5b-9 (in vitro) and in the renal tissues of rats with Thy-1N (in vivo). The in vitro studies demonstrated that IRF-1-enhanced XAF1 gene activation and its regulation by p300-mediated IRF-1 acetylation were involved in GMC apoptosis induced by sublytic C5b-9. The element of IRF-1 binding to XAF1 promoter and two acetylated sites of IRF-1 protein were also revealed. In vivo, silence of p300, IRF-1 or XAF1 genes in the renal tissues diminished GMC apoptosis and secondary GMC proliferation as well as urinary protein secretion in Thy-1N rats. Together, these data implicate that sublytic C5b-9 induces the expression of both p300 and IRF-1, as well as p300-dependent IRF-1 acetylation that may contribute to XAF1 gene activation and subsequent GMC apoptosis in Thy-1N rats.
authors.affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: W
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: G
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: D
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: F
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: T
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000107:Acetylation; D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000473:pathology / Q000648:ultrastructure; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D050527:Mesangial Cells / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D051381:Rats; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D015938:Complement Membrane Attack Complex; D050856:Interferon Regulatory Factor-1; D047908:Intracellular Signaling Peptides and Proteins; D050881:E1A-Associated p300 Protein; C494362:Ep300 protein, rat
references.citation: J Nutr Biochem. 2012 Oct;23(10):1277-84
references.pmid: 22209681
references.citation: BMC Nephrol. 2011 Nov 23;12:64
references.pmid: 22111871
references.citation: J Biol Chem. 2001 Jun 15;276(24):20973-80
references.pmid: 11304541
references.citation: J Cell Biochem. 2011 Feb;112(2):589-99
references.pmid: 21268080
references.citation: J Immunol. 1997 May 1;158(9):4405-12
references.pmid: 9127005
references.citation: Cell Cycle. 2012 Jul 1;11(13):2458-66
references.pmid: 22713239
references.citation: J Physiol Pharmacol. 2012 Aug;63(4):397-401
references.pmid: 23070089
references.citation: Exp Mol Pathol. 2009 Apr;86(2):87-94
references.pmid: 19162005
references.citation: Clin J Am Soc Nephrol. 2007 Sep;2(5):1054-61
references.pmid: 17702711
references.citation: J Pathol. 2012 Mar;226(4):619-32
references.pmid: 21984198
references.citation: J Biol Chem. 2012 Aug 31;287(36):30800-11
references.pmid: 22807441
references.citation: Immunobiology. 2011 Aug;216(8):871-81
references.pmid: 21396734
references.citation: J Biol Chem. 2012 May 11;287(20):16410-23
references.pmid: 22427665
references.citation: Cancer Lett. 2012 Aug 1;321(1):45-54
references.pmid: 22429998
references.citation: PLoS One. 2012;7(7):e42020
references.pmid: 22860050
references.citation: Am J Physiol Renal Physiol. 2011 Feb;300(2):F488-98
references.pmid: 21048020
references.citation: Nephrol Dial Transplant. 2009 Mar;24(3):886-91
references.pmid: 18842673
references.citation: Shock. 2011 Mar;35(3):293-301
references.pmid: 20856174
references.citation: J Biol Chem. 2012 Apr 13;287(16):12622-33
references.pmid: 22367195
references.citation: J Immunol. 2012 Jun 1;188(11):5547-60
references.pmid: 22544934
references.citation: J Biol Chem. 2012 Mar 2;287(10):7026-38
references.pmid: 22241478
references.citation: J Immunol. 2006 Mar 1;176(5):3173-80
references.pmid: 16493077
references.citation: J Nephrol. 2012 Jul-Aug;25(4):566-76
references.pmid: 21983986
references.citation: J Immunol. 1987 Jun 1;138(11):3758-65
references.pmid: 3495569
references.citation: Am J Dermatopathol. 2013 Oct;35(7):722-30
references.pmid: 23392134
references.citation: Neuroscience. 2013 Sep 17;248:681-9
references.pmid: 23811396
references.citation: Kidney Int. 2001 Mar;59(3):905-12
references.pmid: 11231345
references.citation: Cell Physiol Biochem. 2011;27(3-4):391-400
references.pmid: 21471728
references.citation: Mol Med Rep. 2013 Feb;7(2):445-8
references.pmid: 23241730
references.citation: J Virol Methods. 2010 Oct;169(1):112-8
references.pmid: 20637238
references.citation: Clin Nephrol. 2006 Jun;65(6):385-92
references.pmid: 16792132
references.citation: PLoS One. 2012;7(7):e42253
references.pmid: 22860098
references.citation: Lab Invest. 2008 Apr;88(4):387-97
references.pmid: 18268475
references.citation: World J Gastroenterol. 2012 Jun 14;18(22):2844-9
references.pmid: 22719195
references.citation: J Am Soc Nephrol. 1999 Jun;10(6):1242-52
references.pmid: 10361862
references.citation: Mol Biol Cell. 2009 Jan;20(1):419-27
references.pmid: 18987336
references.citation: Am J Physiol Renal Physiol. 2005 Sep;289(3):F593-603
references.pmid: 15855657
references.citation: Mol Cell Biol. 2004 Nov;24(22):10083-98
references.pmid: 15509808
references.citation: Cancer. 2010 Mar 1;116(5):1252-63
references.pmid: 20082449
references.citation: Carcinogenesis. 2009 Feb;30(2):222-9
references.pmid: 19056926
references.citation: Mol Immunol. 2008 Apr;45(8):2236-46
references.pmid: 18178252
references.citation: PLoS Genet. 2012;8(6):e1002769
references.pmid: 22737084
references.citation: Cell Tissue Res. 2006 Oct;326(1):159-68
references.pmid: 16736195
references.citation: Scand J Urol Nephrol. 2008;42(4):373-80
references.pmid: 19230171
references.citation: Cell Death Differ. 2010 Apr;17(4):699-709
references.pmid: 19851330
references.citation: Nephron. 2000 Oct;86(2):152-60
references.pmid: 11014985
references.citation: J Cell Sci. 2013 Jul 1;126(Pt 13):2903-13
references.pmid: 23613465
references.citation: Kidney Int. 1999 Aug;56(2):538-48
references.pmid: 10432393
references.citation: PLoS Biol. 2012;10(2):e1001268
references.pmid: 22389628
references.citation: PLoS One. 2013 Jun 24;8(6):e66759
references.pmid: 23826128
references.citation: PLoS Biol. 2013 Sep;11(9):e1001647
references.pmid: 24019758
references.citation: Eur J Immunol. 2009 Nov;39(11):3251-66
references.pmid: 19882653
references.citation: PLoS One. 2011 Mar 22;6(3):e17929
references.pmid: 21445358
references.citation: Life Sci. 2006 Jun 6;79(2):182-92
references.pmid: 16458938
references.citation: Oncogene. 2011 Jan 27;30(4):482-93
references.pmid: 20856196
references.citation: Adv Exp Med Biol. 2012;723:23-30
references.pmid: 22183311
references.citation: Kidney Int. 2012 Dec;82(12):1284-96
references.pmid: 22951891
references.citation: Regul Pept. 2012 Oct 10;178(1-3):36-42
references.pmid: 22759793
references.citation: Mol Carcinog. 2012 May;51(5):422-32
references.pmid: 21678496
references.citation: Mol Immunol. 2011 Sep;48(15-16):2151-8
references.pmid: 21821293