Appearance of tissue transglutaminase in astrocytes in multiple sclerosis lesions: a role in cell adhesion and migration?
Multiple Sclerosis (MS) is a neuroinflammatory disease mainly affecting young adults. A major pathological hallmark of MS is the presence of demyelinated lesions in the central nervous system. In the active phase of the disease, astrocytes become activated, migrate and contribute to local tissue remodeling that ultimately can result in an astroglial scar. This process is facilitated by extracellular matrix proteins, including fibronectin. Tissue Transglutaminase (TG2) is a multifunctional enzyme with a ubiquitous tissue distribution and it has been shown that inflammatory cytokines can induce TG2 activity. In addition, TG2 is known to mediate cell adhesion and migration. We therefore hypothesized that TG2 is present in MS lesions and plays a role in cell adhesion and/or migration. Our studies showed that TG2 immunoreactivity appeared in astrocytes in active and chronic active MS lesions. These TG2 positive astrocytes partly co-localized with fibronectin. Additional in vitro studies showed that TG2 mediated astrocytoma adhesion to and migration on the extracellular matrix protein fibronectin. We therefore speculate that TG2 mediates the enhanced interaction of astrocytes with fibronectin in the extracellular matrix of MS lesions, thereby contributing to astrocyte adhesion and migration, and thus in tissue remodeling and possibly glial scarring.
van Strien
Miriam E
ME
VU University Medical Center, Neuroscience Campus Amsterdam, Department of Anatomy & Neurosciences Pathology Molecular Cell Biology and Immunology, Amsterdam, The Netherlands.
Drukarch
Benjamin
B
Bol
John G
JG
van der Valk
Paul
P
van Horssen
Jack
J
Gerritsen
Wouter H
WH
Breve
John J
JJ
van Dam
Anne-Marie
AM
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D019204:GTP-Binding Proteins; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000201:enzymology* / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D034741:RNA, Small Interfering; D011503:Transglutaminases / Q000378:metabolism*
D005353:Fibronectins; D034741:RNA, Small Interfering; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins