title: Tumor Necrosis Factor-stimulated Gene-6 (TSG-6) Is Constitutively Expressed in Adult Central Nervous System (CNS) and Associated with Astrocyte-mediated Glial Scar Formation following Spinal Cord Injury.
abstract: Tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) binds to hyaluronan and can reorganize/stabilize its structure, also enhancing the binding of this glycosaminoglycan to its cell surface receptor, CD44. TSG-6 is rapidly up-regulated in response to inflammatory cytokines protecting tissues from the damaging effects of inflammation. Despite TSG-6 treatment having been shown to improve outcomes in an experimental model of traumatic brain injury, TSG-6 expression has not been extensively studied in the central nervous system (CNS). We hereby analyzed the expression profile of TSG-6 in the developing CNS and following injury. We show that TSG-6 is expressed in the rat CNS by GFAP(+) and CD44(+) astrocytes, solely in the mature brain and spinal cord, and is not present during the development of the CNS. TSG-6(-/-) mice present a reduced number of GFAP(+) astrocytes when compared with the littermate TSG-6(+/-) mice. TSG-6 expression is drastically up-regulated after injury, and the TSG-6 protein is present within the glial scar, potentially coordinating and stabilizing the formation of this hyaluronan-rich matrix. This study shows that TSG-6 is expressed in the CNS, suggesting a role for TSG-6 in astrocyte activation and tissue repair. We hypothesize that within this context TSG-6 could participate in the formation of the glial scar and confer anti-inflammatory properties. Further studies are required to elucidate the therapeutic potential of targeting TSG-6 after CNS injury to promote its protective effects while reducing the inhibitory properties of the glial scar in axon regeneration.
authors.affiliation: From the John Van Geest Cambridge Centre for Brain Repair, The E. D. Adrian Building, Forvie Site, Robinson Way, University of Cambridge, Cambridge CB2 0PY, United Kingdom, vcoulsonthomas@gmail.com.
authors.forename: Vivien J
authors.initials: VJ
authors.lastname: Coulson-Thomas
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio 44195.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lauer
authors.affiliation: From the John Van Geest Cambridge Centre for Brain Repair, The E. D. Adrian Building, Forvie Site, Robinson Way, University of Cambridge, Cambridge CB2 0PY, United Kingdom.
authors.forename: Sara
authors.initials: S
authors.lastname: Soleman
authors.affiliation: Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge CB2 0AH, United Kingdom, and.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio 44195.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Hascall
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom anthony.day@manchester.ac.uk.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Day
authors.affiliation: From the John Van Geest Cambridge Centre for Brain Repair, The E. D. Adrian Building, Forvie Site, Robinson Way, University of Cambridge, Cambridge CB2 0PY, United Kingdom, jf108@cam.ac.uk.
authors.forename: James W
authors.initials: JW
authors.lastname: Fawcett
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002921:Cicatrix / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D015815:Cell Adhesion Molecules; D009419:Nerve Tissue Proteins; C513057:Tnfaip6 protein, mouse
keywords: astrocyte; glial scar; glycosaminoglycan; hyaluronan; inflammation; proteoglycan