Tenascin-R plays a role in neuroprotection via its distinct domains that coordinate to modulate the microglia function.
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.
Liao
Hong
H
Department of Clinical Research, Singapore General Hospital, Singapore 169609.
Bu
Wen-yu
WY
Wang
Ting-Hua
TH
Ahmed
Sohail
S
Xiao
Zhi-Cheng
ZC
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
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