Astrocyte-derived tissue Transglutaminase affects fibronectin deposition, but not aggregation, during cuprizone-induced demyelination
| Autor: | John G.J.M. Bol, Anne Marie Van Dam, Wia Baron, Benjamin Drukarch, Berta Sanz-Morello, John J. P. Brevé, Jan Bauer, Nathaly Espitia Pinzon |
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| Přispěvatelé: | Anatomy and neurosciences, Amsterdam Neuroscience - Neuroinfection & -inflammation, Molecular Neuroscience and Ageing Research (MOLAR) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
GROWTH-FACTOR CROSS-LINKING Tissue transglutaminase Biology Blood–brain barrier Protein Aggregation Pathological Article Glial scar Corpus Callosum Extracellular matrix REMYELINATION 03 medical and health sciences Cuprizone Mice 0302 clinical medicine GTP-Binding Proteins medicine EXTRACELLULAR-MATRIX Animals Protein Glutamine gamma Glutamyltransferase 2 Remyelination Chelating Agents Mice Knockout Multidisciplinary Transglutaminases BLOOD-BRAIN-BARRIER CENTRAL-NERVOUS-SYSTEM MULTIPLE-SCLEROSIS LESIONS medicine.disease Cell biology Astrogliosis Fibronectins Fibronectin 030104 developmental biology medicine.anatomical_structure GLIAL SCAR AXONAL LOSS Astrocytes Immunology biology.protein 030217 neurology & neurosurgery CELL-ADHESION Astrocyte Demyelinating Diseases |
| Zdroj: | Scientific Reports Scientific Reports, 7:40995. Nature Publishing Group Espitia Pinzon, N, Sanz-Morello, B, Brevé, J J P, Bol, J G J M, Drukarch, B, Bauer, J, Baron, W & Van Dam, A M 2017, ' Astrocyte-derived tissue Transglutaminase affects fibronectin deposition, but not aggregation, during cuprizone-induced demyelination ', Scientific Reports, vol. 7, 40995 . https://doi.org/10.1038/srep40995 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep40995 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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