title: Astrocyte-derived tissue Transglutaminase affects fibronectin deposition, but not aggregation, during cuprizone-induced demyelination.
abstract: Astrogliosis as seen in Multiple Sclerosis (MS) develops into astroglial scarring, which is beneficial because it seals off the site of central nervous system (CNS) damage. However, astroglial scarring also forms an obstacle that inhibits axon outgrowth and (re)myelination in brain lesions. This is possibly an important cause for incomplete remyelination in the CNS of early stage MS patients and for failure in remyelination when the disease progresses. In this study we address whether under demyelinating conditions in vivo, tissue Transglutaminase (TG2), a Ca2+-dependent enzyme that catalyses posttranslational modification of proteins, contributes to extracellular matrix (ECM) deposition and/or aggregation. We used the cuprizone model for de- and remyelination. TG2 immunoreactivity and enzymatic activity time-dependently appeared in astrocytes and ECM, respectively, in the corpus callosum of cuprizone-treated mice. Enhanced presence of soluble monomeric and multimeric fibronectin was detected during demyelination, and fibronectin immunoreactivity was slightly decreased in cuprizone-treated TG2-/-mice. In vitro TG2 overexpression in astrocytes coincided with more, while knock-down of TG2 with less fibronectin production. TG2 contributes, at least partly, to fibronectin production, and may play a role in fibronectin deposition during cuprizone-induced demyelination. Our observations are of interest in understanding the functional implications of TG2 during astrogliosis.
authors.affiliation: VU University Medical Center, Neuroscience Campus Amsterdam, Dept. Anatomy and Neurosciences, Amsterdam, 1081 HV, The Netherlands.
authors.forename: Nathaly
authors.initials: N
authors.lastname: Espitia Pinzon
authors.affiliation: VU University Medical Center, Neuroscience Campus Amsterdam, Dept. Anatomy and Neurosciences, Amsterdam, 1081 HV, The Netherlands.
authors.forename: Berta
authors.initials: B
authors.lastname: Sanz-Morello
authors.affiliation: VU University Medical Center, Neuroscience Campus Amsterdam, Dept. Anatomy and Neurosciences, Amsterdam, 1081 HV, The Netherlands.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Brevé
authors.affiliation: VU University Medical Center, Neuroscience Campus Amsterdam, Dept. Anatomy and Neurosciences, Amsterdam, 1081 HV, The Netherlands.
authors.forename: John G J M
authors.initials: JG
authors.lastname: Bol
authors.affiliation: VU University Medical Center, Neuroscience Campus Amsterdam, Dept. Anatomy and Neurosciences, Amsterdam, 1081 HV, The Netherlands.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Drukarch
authors.affiliation: Center for Brain Research, Dept. Neuroimmunology, Vienna, A-1090, Austria.
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.affiliation: University Medical Center Groningen, Dept. of Cell Biology, Groningen, 9713 AV, The Netherlands.
authors.forename: Wia
authors.initials: W
authors.lastname: Baron
authors.affiliation: VU University Medical Center, Neuroscience Campus Amsterdam, Dept. Anatomy and Neurosciences, Amsterdam, 1081 HV, The Netherlands.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: van Dam
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D002614:Chelating Agents / Q000633:toxicity*; D003337:Corpus Callosum / Q000473:pathology; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced*; D005353:Fibronectins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D066263:Protein Aggregation, Pathological; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D005353:Fibronectins; D003471:Cuprizone; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins