title: TGF-β superfamily gene expression and induction of the Runx1 transcription factor in adult neurogenic regions after brain injury.
abstract: Traumatic brain injury (TBI) increases neurogenesis in the forebrain subventricular zone (SVZ) and the hippocampal dentate gyrus (DG). Transforming growth factor-β (TGF-β) superfamily cytokines are important regulators of adult neurogenesis, but their involvement in the regulation of this process after brain injury is unclear. We subjected adult mice to controlled cortical impact (CCI) injury, and isolated RNA from the SVZ and DG at different post-injury time points. qPCR array analysis showed that cortical injury caused significant alterations in the mRNA expression of components and targets of the TGF-β, BMP, and activin signaling pathways in the SVZ and DG after injury, suggesting that these pathways could regulate post-injury neurogenesis. In both neurogenic regions, the injury also induced expression of Runt-related transcription factor-1 (Runx1), which can interact with intracellular TGF-β Smad signaling pathways. CCI injury strongly induced Runx1 expression in activated and proliferating microglial cells throughout the neurogenic regions. Runx1 protein was also expressed in a subset of Nestin- and GFAP-expressing putative neural stem or progenitor cells in the DG and SVZ after injury. In the DG only, these Runx1+ progenitors proliferated. Our data suggest potential roles for Runx1 in the processes of microglial cell activation and proliferation and in neural stem cell proliferation after TBI.
authors.affiliation: Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Trevor T
authors.initials: TT
authors.lastname: Logan
authors.forename: Sonia
authors.initials: S
authors.lastname: Villapol
authors.forename: Aviva J
authors.initials: AJ
authors.lastname: Symes
mesh_terms: D028341:Activins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001930:Brain Injuries / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000293:injuries / Q000378:metabolism*; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000293:injuries / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C493726:Runx1 protein, mouse; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C528900:glial fibrillary astrocytic protein, mouse; D028341:Activins
references.citation: J Rehabil Res Dev. 2009;46(6):655-66
references.pmid: 20104395
references.citation: Int J Dev Biol. 2010;54(6-7):1151-63
references.pmid: 20711992
references.citation: Neurotherapeutics. 2010 Oct;7(4):366-77
references.pmid: 20880501
references.citation: Exp Mol Med. 2004 Jun 30;36(3):211-9
references.pmid: 15272232
references.citation: Neuron. 2011 May 26;70(4):687-702
references.pmid: 21609825
references.citation: Discov Med. 2010 Nov;10(54):434-42
references.pmid: 21122475
references.citation: Stem Cells. 2011 Jun;29(6):907-12
references.pmid: 21557389
references.citation: Mol Cell Neurosci. 2012 Jan;49(1):23-31
references.pmid: 21906677
references.citation: Neuroimmunomodulation. 2010;17(3):200-1
references.pmid: 20134202
references.citation: Mol Cell Biol. 2000 Jan;20(1):319-28
references.pmid: 10594034
references.citation: Med Sci (Paris). 2011 Aug-Sep;27(8-9):719-24
references.pmid: 21880259
references.citation: J Biol Chem. 2000 Feb 4;275(5):3438-45
references.pmid: 10652337
references.citation: PLoS One. 2009 Oct 20;4(10):e7506
references.pmid: 19841742
references.citation: J Neurosci. 2008 Nov 26;28(48):12901-12
references.pmid: 19036984
references.citation: J Neurosci. 2005 Feb 23;25(8):2050-61
references.pmid: 15728845
references.citation: Stroke. 2003 Feb;34(2):558-64
references.pmid: 12574575
references.citation: J Neurosci. 2012 Aug 15;32(33):11285-98
references.pmid: 22895712
references.citation: Exp Neurol. 2012 May;235(1):336-44
references.pmid: 22414310
references.citation: Neuron. 2006 Feb 2;49(3):365-77
references.pmid: 16446141
references.citation: Exp Hematol. 2010 May;38(5):403-16
references.pmid: 20206228
references.citation: EMBO J. 1995 Feb 15;14(4):736-42
references.pmid: 7882977
references.citation: J Thromb Haemost. 2005 Jul;3(7):1379-84
references.pmid: 15978095
references.citation: J Neurosci Res. 2010 Aug 15;88(11):2441-9
references.pmid: 20623540
references.citation: Blood. 2011 Dec 15;118(25):6626-37
references.pmid: 22021368
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6451-6
references.pmid: 18427115
references.citation: Prog Brain Res. 2007;161:81-95
references.pmid: 17618971
references.citation: J Neuroinflammation. 2012 Jun 29;9:149
references.pmid: 22747686
references.citation: PLoS One. 2008 Apr 02;3(4):e1869
references.pmid: 18382659
references.citation: Am J Pathol. 2006 Jul;169(1):154-64
references.pmid: 16816369
references.citation: Biochem Biophys Res Commun. 2001 Mar;281(5):1248-55
references.pmid: 11243869
references.citation: Brain Behav Immun. 2010 Nov;24(8):1301-9
references.pmid: 20600816
references.citation: Stem Cells. 2007 Dec;25(12):3204-14
references.pmid: 17872503
references.citation: J Neurochem. 2011 Mar;116(6):947-56
references.pmid: 21198642
references.citation: J Neuropathol Exp Neurol. 2010 Jul;69(7):717-28
references.pmid: 20535034
references.citation: Mol Cell Neurosci. 2002 Dec;21(4):634-44
references.pmid: 12504596
references.citation: J Neurosci. 2011 Mar 30;31(13):4906-16
references.pmid: 21451029
references.citation: Int J Biochem Cell Biol. 2007;39(12):2183-94
references.pmid: 17659994
references.citation: Neuron. 2000 Dec;28(3):713-26
references.pmid: 11163261
references.citation: J Biol Chem. 2000 Dec 22;275(51):40282-7
references.pmid: 11032826
references.citation: J Biol Chem. 1999 Oct 29;274(44):31577-82
references.pmid: 10531362
references.citation: Science. 2010 Nov 5;330(6005):841-5
references.pmid: 20966214
references.citation: Stroke. 2012 Oct;43(10):2833-9
references.pmid: 22879095
references.citation: Glia. 2006 Sep;54(4):329-42
references.pmid: 16862532
references.citation: Cell Stem Cell. 2007 Nov;1(5):515-28
references.pmid: 18371391
references.citation: J Biol Chem. 2004 Apr 9;279(15):15678-87
references.pmid: 14747476
references.citation: J Cell Physiol. 2009 Jun;219(3):520-4
references.pmid: 19235904
references.citation: Curr Opin Neurobiol. 1999 Feb;9(1):135-41
references.pmid: 10072370
references.citation: Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1477-97
references.pmid: 16939970
references.citation: Scand J Trauma Resusc Emerg Med. 2012 Feb 03;20:12
references.pmid: 22304785
references.citation: J Mol Neurosci. 2013 May;50(1):109-23
references.pmid: 22936246
references.citation: Neuroscience. 2009 Feb 6;158(3):1021-9
references.pmid: 18662748
references.citation: Neurobiol Dis. 2010 Feb;37(2):267-74
references.pmid: 19909815
references.citation: J Neuropathol Exp Neurol. 2006 Apr;65(4):358-70
references.pmid: 16691117
references.citation: PLoS One. 2010 Nov 11;5(11):e13944
references.pmid: 21085653
references.citation: Adv Clin Chem. 2007;43:117-30
references.pmid: 17249382
references.citation: J Neurosurg. 2010 May;112(5):1125-38
references.pmid: 19499984
references.citation: BMC Neurosci. 2006 Sep 20;7:64
references.pmid: 16987412
references.citation: Stem Cells. 2009 Jun;27(6):1330-46
references.pmid: 19489097
references.citation: Int J Crit Illn Inj Sci. 2011 Jan;1(1):27-35
references.pmid: 22096771
references.citation: Eur J Neurosci. 2011 Mar;33(6):1025-36
references.pmid: 21395845
references.citation: Eur J Neurosci. 2006 Aug;24(3):661-75
references.pmid: 16930398
references.citation: Exp Neurol. 2009 Oct;219(2):516-23
references.pmid: 19615997
references.citation: BMC Neurosci. 2008 Dec 10;9:117
references.pmid: 19077183
references.citation: Cell Tissue Res. 2012 Jan;347(1):187-201
references.pmid: 21850492
references.citation: Oncogene. 1997 Sep;15(11):1315-27
references.pmid: 9315100
references.citation: J Neurotrauma. 2005 Jun;22(6):645-55
references.pmid: 15941374
references.citation: Brain Res Mol Brain Res. 2002 Oct 30;107(1):57-64
references.pmid: 12414124
references.citation: Brain. 2012 Nov;135(Pt 11):3251-64
references.pmid: 22822039
references.citation: Eur J Neurosci. 2006 Jan;23(1):83-93
references.pmid: 16420418
references.citation: J Neurotrauma. 2011 Jun;28(6):995-1007
references.pmid: 21463148
references.citation: Oncogene. 2004 May 24;23(24):4232-7
references.pmid: 15156178
references.citation: Cell Stem Cell. 2010 Jul 2;7(1):78-89
references.pmid: 20621052
references.citation: Nat Med. 2002 Sep;8(9):963-70
references.pmid: 12161747
references.citation: Stroke. 2001 Sep;32(9):2170-8
references.pmid: 11546913
references.citation: Neuron. 2011 May 26;70(4):674-86
references.pmid: 21609824
references.citation: J Neurosci. 2008 Sep 10;28(37):9194-204
references.pmid: 18784300
references.citation: J Mol Neurosci. 2010 Jul;41(3):383-96
references.pmid: 20155334