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

Y. K J Leung, M. Pankhurst, S. A. Dunlop, S. Ray, J. Dittmann, E. D. Eaton, P. Palumaa, R. Sillard, M. I. Chuah, A. K. West, R. S. Chung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

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. Crown

Original languageEnglish
Pages (from-to)98-106
Number of pages9
JournalExperimental Neurology
Volume221
Issue number1
DOIs
Publication statusPublished - Jan 2010
Externally publishedYes

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