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Metallothionein induces a regenerative reactive astrocyte phenotype via JAK/STAT and RhoA signalling pathways

Citation

Leung, YKJ and Pankhurst, M and Dunlop, SA and Ray, S and Dittmann, J and Eaton, ED and Palumaa, P and Sillard, R and Chuah, MI and West, AK and Chung, RS, Metallothionein induces a regenerative reactive astrocyte phenotype via JAK/STAT and RhoA signalling pathways , Experimental Neurology: A Journal of Neuroscience Research, 221, (1) pp. 98-106. ISSN 0014-4886 (2010) [Refereed Article]


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DOI: doi:10.1016/j.expneurol.2009.10.006

Abstract

Following central nervous system injury, astrocytes rapidly respond by undergoing a stereotypical pattern of molecular and morphological alterations termed "reactive" astrogliosis. We have reported previously that metallothioneins (MTs) are rapidly expressed by reactive astrocytes and that their secretion and subsequent interaction with injured neurons leads to improved neuroregeneration. We now demonstrate that exogenous MT induces a reactive morphology and elevated GFAP expression in cultured astrocytes. Furthermore, these astrogliotic hallmarks were mediated via JAK/STAT and RhoA signalling pathways. However, rather than being inhibitory, MT induced a form of astrogliosis that was permissive to neurite outgrowth and which was associated with decreased chondroitin sulphate proteoglycan (CSPG) expression. The results suggest that MT has an important role in mediating permissive astrocytic responses to traumatic brain injury.

Item Details

Item Type:Refereed Article
Keywords:Traumatic brain injury, Astrogliosis, Regeneration
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Leung, YKJ (Dr Jacqueline Leung)
Author:Pankhurst, M (Mr Michael Pankhurst)
Author:Ray, S (Mrs Shannon Huskins)
Author:Dittmann, J (Mr Justin Dittmann)
Author:Eaton, ED (Dr Emma Eaton)
Author:Chuah, MI (Dr Inn Chuah)
Author:West, AK (Professor Adrian West)
Author:Chung, RS (Associate Professor Roger Chung)
ID Code:64815
Year Published:2010
Web of Science® Times Cited:37
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-09-02
Last Modified:2011-04-29
Downloads:0

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