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Originally published In Press as doi:10.1074/jbc.M412730200 on December 22, 2004

J. Biol. Chem., Vol. 280, Issue 9, 8316-8323, March 4, 2005
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Tenascin-R Plays a Role in Neuroprotection via Its Distinct Domains That Coordinate to Modulate the Microglia Function*

Hong Liao{ddagger}, Wen-yu Bu§, Ting-Hua Wang¶, Sohail Ahmed§, and Zhi-Cheng Xiao{ddagger}||**

From the {ddagger}Department of Clinical Research, Singapore General Hospital, Singapore 169609, §Centre for Molecular Medicine, Singapore 117609, Department of Histology, Embryology and Neurobiology, College of Preclinical and Forensic Medicine, Sichuan University, Chendu, China 610065, and ||Institute of Molecular and Cell Biology, Singapore 117609

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.


Received for publication, November 10, 2004

* This work was supported by grants from the National Medical Research Council of Singapore, Singapore Health Service Pte Ltd., and Department of Clinical Research, Singapore General Hospital (to Z.-C. X.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

** To whom correspondence should be addressed: Neurobiology Laboratory, Dept. of Clinical Research, Singapore General Hospital, Block A, No. 7 Hospital Dr., Singapore 169608. Tel.: 65-6326-6195; Fax: 65-6321-3606; E-mail: gcrxzc{at}sgh.com.sg.


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