title: Tenascin-R plays a role in neuroprotection via its distinct domains that coordinate to modulate the microglia function.
abstract: Microglia are one of the main cell types activated by brain injury. In the present study, we have investigated how domains of the extracellular matrix molecule tenascin-R (TN-R) modulate microglia function. We found that epidermal growth factor-like repeats inhibited adhesion and migration of microglia via a protein kinase A-dependent mechanism. In contrast, fibronectin 6-8 repeats promoted adhesion and migration of the primary microglia via a protein kinase C-dependent mechanism. Both domains of TN-R induced an up-regulation in the secretion of cytokines, such as chemokine-induced cytokine 3 and tumor neurosis factor alpha. Interestingly, epidermal growth factor-like repeats and fibronectin 6-8 induced a dramatic up-regulation in the secretion of brain-derived neurotrophic factor/transforming growth factor-beta and nerve growth factor/transforming growth factor-beta, respectively, and conditioned medium from activated microglia was able to promote neurite outgrowth of N1E-115 cells and primary cortical neurons. These results suggest that TN-R plays a role in neuroprotection through distinct domains coordinating to modulate microglia function.
authors.affiliation: Department of Clinical Research, Singapore General Hospital, Singapore 169609.
authors.forename: Hong
authors.initials: H
authors.lastname: Liao
authors.forename: Wen-yu
authors.initials: WY
authors.lastname: Bu
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
authors.forename: Sohail
authors.initials: S
authors.lastname: Ahmed
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D017628:Microglia / Q000378:metabolism*; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D019063:Tenascin / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017077:Culture Media, Conditioned; D016207:Cytokines; D005353:Fibronectins; D006133:Growth Substances; D011993:Recombinant Fusion Proteins; D019063:Tenascin; D016212:Transforming Growth Factor beta; C074638:tenascin R; D004815:Epidermal Growth Factor; D005982:Glutathione Transferase; D017868:Cyclic AMP-Dependent Protein Kinases