title: Astrocyte-derived tissue transglutaminase interacts with fibronectin: a role in astrocyte adhesion and migration?
abstract: An important neuropathological feature of neuroinflammatory processes that occur during e.g. Multiple Sclerosis (MS) is the formation of an astroglial scar. Astroglial scar formation is facilitated by the interaction between astrocytes and extracellular matrix proteins (ECM) such as fibronectin. Since there is evidence indicating that glial scars strongly inhibit both axon growth and (re)myelination in brain lesions, it is important to understand the factors that contribute to the interaction between astrocytes and ECM proteins. Tissue Transglutaminase (TG2) is a multifunctional enzyme with an ubiquitous tissue distribution, being clearly present within the brain. It has been shown that inflammatory cytokines can enhance TG2 activity. In addition, TG2 can mediate cell adhesion and migration and it binds fibronectin with high affinity. We therefore hypothesized that TG2 is involved in astrocyte-fibronectin interactions. Our studies using primary rat astrocytes show that intracellular and cell surface expression and activity of TG2 is increased after treatment with pro-inflammatory cytokines. Astrocyte-derived TG2 interacts with fibronectin and is involved in astrocyte adhesion onto and migration across fibronectin. TG2 is involved in stimulating focal adhesion formation which is necessary for the interaction of astrocytes with ECM proteins. We conclude that astrocyte-derived TG2 contributes to the interaction between astrocytes and fibronectin. It might thereby regulate ECM remodeling and possibly glial scarring.
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Miriam E
authors.initials: ME
authors.lastname: van Strien
authors.forename: John J P
authors.initials: JJ
authors.lastname: Brevé
authors.forename: Silvina
authors.initials: S
authors.lastname: Fratantoni
authors.forename: Marco W J
authors.initials: MW
authors.lastname: Schreurs
authors.forename: John G J M
authors.initials: JG
authors.lastname: Bol
authors.forename: Cornelis A M
authors.initials: CA
authors.lastname: Jongenelen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Drukarch
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: van Dam
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix; D005353:Fibronectins / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D012333:RNA, Messenger; C000717609:Tgm2 protein, rat; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins