Astrocyte-derived tissue Transglutaminase interacts with fibronectin: a role in glia adhesion and migration?

An important neuropathological feature of brain injury and neuroinflammation, including 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 mediate scar formation. Tissue Transglutaminase (TG2) is a multifunctional enzyme with a ubiquitous tissue distribution, being clearly present within the brain. It has been shown that inflammatory cytokines can induce 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-ECM 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. TG2 on the surface of astrocytes interacts with fibronectin and is involved in astrocytic adhesion to fibronectin. TG2 is an essential factor in stimulating focal adhesion formation which is necessary for interaction of astrocytes with the ECM. We conclude that astrocyte-derived surface TG2 contributes to the interaction between astrocytes and fibronectin, thereby regulating ECM remodeling and possibly glial scarring.