title: Immune response and mitochondrial metabolism are commonly deregulated in DMD and aging skeletal muscle.
abstract: Duchenne Muscular Dystrophy (DMD) is a complex process involving multiple pathways downstream of the primary genetic insult leading to fatal muscle degeneration. Aging muscle is a multifactorial neuromuscular process characterized by impaired muscle regeneration leading to progressive atrophy. We hypothesized that these chronic atrophying situations may share specific myogenic adaptative responses at transcriptional level according to tissue remodeling. Muscle biopsies from four young DMD and four AGED subjects were referred to a group of seven muscle biopsies from young subjects without any neuromuscular disorder and explored through a dedicated expression microarray. We identified 528 differentially expressed genes (out of 2,745 analyzed), of which 328 could be validated by an exhaustive meta-analysis of public microarray datasets referring to DMD and Aging in skeletal muscle. Among the 328 validated co-expressed genes, 50% had the same expression profile in both groups and corresponded to immune/fibrosis responses and mitochondrial metabolism. Generalizing these observed meta-signatures with large compendia of public datasets reinforced our results as they could be also identified in other pathological processes and in diverse physiological conditions. Focusing on the common gene signatures in these two atrophying conditions, we observed enrichment in motifs for candidate transcription factors that may coordinate either the immune/fibrosis responses (ETS1, IRF1, NF1) or the mitochondrial metabolism (ESRRA). Deregulation in their expression could be responsible, at least in part, for the same transcriptome changes initiating the chronic muscle atrophy. This study suggests that distinct pathophysiological processes may share common gene responses and pathways related to specific transcription factors.
authors.affiliation: INSERM, UMR915, Nantes, France. daniel.baron@inserm.fr
authors.forename: Daniel
authors.initials: D
authors.lastname: Baron
authors.forename: Armelle
authors.initials: A
authors.lastname: Magot
authors.forename: Gérard
authors.initials: G
authors.lastname: Ramstein
authors.forename: Marja
authors.initials: M
authors.lastname: Steenman
authors.forename: Guillemette
authors.initials: G
authors.lastname: Fayet
authors.forename: Catherine
authors.initials: C
authors.lastname: Chevalier
authors.forename: Philippe
authors.initials: P
authors.lastname: Jourdon
authors.forename: Rémi
authors.initials: R
authors.lastname: Houlgatte
authors.forename: Frédérique
authors.initials: F
authors.lastname: Savagner
authors.forename: Yann
authors.initials: Y
authors.lastname: Pereon
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics / Q000502:physiology*; D000293:Adolescent; D000375:Aging / Q000235:genetics; D002648:Child; D016000:Cluster Analysis; D006801:Humans; D066298:In Vitro Techniques; D050856:Interferon Regulatory Factor-1 / Q000235:genetics; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000276:immunology* / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D025542:Neurofibromin 1 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D050856:Interferon Regulatory Factor-1; D025542:Neurofibromin 1; D050784:Proto-Oncogene Protein c-ets-1; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor; C494041:ETS1 protein, human; C494257:IRF1 protein, human
references.citation: Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14440-5
references.pmid: 11717410
references.citation: Dev Dyn. 1995 Mar;202(3):302-11
references.pmid: 7780179
references.citation: Bioinformatics. 2005 Jan 15;21(2):171-8
references.pmid: 15308542
references.citation: Lancet. 2005 Feb 5-11;365(9458):488-92
references.pmid: 15705458
references.citation: Eur J Heart Fail. 2005 Mar 2;7(2):157-65
references.pmid: 15701461
references.citation: Physiology (Bethesda). 2008 Jun;23:160-70
references.pmid: 18556469
references.citation: PLoS One. 2009 Oct 01;4(10):e7249
references.pmid: 19794913
references.citation: Neurol Clin. 1998 Aug;16(3):659-69
references.pmid: 9666043
references.citation: BMC Genomics. 2007 Oct 04;8:357
references.pmid: 17916255
references.citation: Genome Res. 2004 Jun;14(6):1085-94
references.pmid: 15173114
references.citation: Nat Med. 1997 Sep;3(9):970-7
references.pmid: 9288722
references.citation: PLoS One. 2008;3(12):e4001
references.pmid: 19104654
references.citation: Gene. 2007 Oct 15;401(1-2):12-8
references.pmid: 17651921
references.citation: Bioinformatics. 2011 Mar 1;27(5):725-6
references.pmid: 21216776
references.citation: Physiol Rev. 2002 Apr;82(2):291-329
references.pmid: 11917091
references.citation: Cancer Res. 2002 Aug 1;62(15):4427-33
references.pmid: 12154050
references.citation: Neuromuscul Disord. 2002 Jun;12(5):484-93
references.pmid: 12031622
references.citation: J Membr Biol. 1993 May;133(3):243-51
references.pmid: 8392585
references.citation: Bioinformatics. 2009 Jun 15;25(12):1543-9
references.pmid: 19376825
references.citation: BMC Bioinformatics. 2008 Dec 18;9:548
references.pmid: 19094235
references.citation: Curr Aging Sci. 2011 Dec;4(3):209-20
references.pmid: 21529328
references.citation: FASEB J. 2004 Jan;18(1):39-51
references.pmid: 14718385
references.citation: Muscle Nerve. 2004 Feb;29(2):191-7
references.pmid: 14755482
references.citation: Mol Cancer. 2003 Aug 20;2:29
references.pmid: 12971829
references.citation: BMC Genomics. 2011 Feb 16;12:113
references.pmid: 21324190
references.citation: Biol Reprod. 2005 Nov;73(5):959-66
references.pmid: 16014816
references.citation: Clin Genet. 2006 Jul;70(1):1-13
references.pmid: 16813595
references.citation: Ann Neurol. 1995 Jan;37(1):24-9
references.pmid: 7818253
references.citation: N Engl J Med. 1996 Dec 19;335(25):1897-905
references.pmid: 8948566
references.citation: J Biol Chem. 2003 Mar 14;278(11):9013-8
references.pmid: 12522104
references.citation: Cytokine. 2010 Apr;50(1):1-14
references.pmid: 20036577
references.citation: Mech Ageing Dev. 1994 Oct 20;76(2-3):215-24
references.pmid: 7885066
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5093-8
references.pmid: 11309484
references.citation: Physiol Genomics. 2005 Aug 11;22(3):283-91
references.pmid: 15855387
references.citation: BMC Med Genomics. 2009 May 28;2:31
references.pmid: 19476647
references.citation: Hum Mol Genet. 1995;4 Spec No:1711-6
references.pmid: 8541869
references.citation: J Natl Cancer Inst. 2007 Jan 17;99(2):147-57
references.pmid: 17227998
references.citation: Free Radic Biol Med. 1998 Nov 15;25(8):964-72
references.pmid: 9840742
references.citation: Exp Gerontol. 2006 Dec;41(12):1234-8
references.pmid: 17052879
references.citation: FASEB J. 2007 Jan;21(1):140-55
references.pmid: 17116744
references.citation: PLoS Med. 2008 Sep 30;5(9):e184
references.pmid: 18767902
references.citation: Nutr Rev. 2003 May;61(5 Pt 1):157-67
references.pmid: 12822704
references.citation: Curr Genomics. 2008 Dec;9(8):525-34
references.pmid: 19516959
references.citation: Endocr Rev. 2008 Oct;29(6):677-96
references.pmid: 18664618
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
references.pmid: 16199517
references.citation: Mol Syst Biol. 2009;5:307
references.pmid: 19756046
references.citation: J Clin Invest. 2000 Jun;105(12):1669-74
references.pmid: 10862780
references.citation: Sports Med. 2004;34(10):663-79
references.pmid: 15335243
references.citation: Ageing Res Rev. 2006 May;5(2):179-95
references.pmid: 16647308
references.citation: FEBS J. 2010 Feb;277(3):713-25
references.pmid: 20067526
references.citation: Hum Mol Genet. 2011 Jul 15;20(14):2697-709
references.pmid: 21478499
references.citation: J Appl Physiol (1985). 2001 Aug;91(2):534-51
references.pmid: 11457764
references.citation: BMC Bioinformatics. 2002;3:4
references.pmid: 11936955
references.citation: PLoS One. 2010 Jul 07;5(7):e11468
references.pmid: 20628647
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D26-31
references.pmid: 17148475
references.citation: Science. 2001 Nov 23;294(5547):1704-8
references.pmid: 11679633
references.citation: J Comput Biol. 2000 Feb-Apr;7(1-2):203-14
references.pmid: 10890397
references.citation: Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3710-4
references.pmid: 8475120
references.citation: J Cell Mol Med. 2010 Jun;14(6B):1443-52
references.pmid: 19793385
references.citation: Brain. 2006 May;129(Pt 5):1249-59
references.pmid: 16537564
references.citation: Nucleic Acids Res. 2004 Oct 08;32(18):5349-58
references.pmid: 15475389
references.citation: Appl Physiol Nutr Metab. 2008 Feb;33(1):124-9
references.pmid: 18347662
references.citation: Proc Natl Acad Sci U S A. 1990 May;87(10):3723-7
references.pmid: 2187191
references.citation: Free Radic Biol Med. 1999 Feb;26(3-4):303-8
references.pmid: 9895220
references.citation: J Gerontol A Biol Sci Med Sci. 1995 Nov;50 Spec No:5-8
references.pmid: 7493218
references.citation: BMC Med Inform Decis Mak. 2006 Jun 21;6:27
references.pmid: 16790051