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

journal contribution
posted on 2023-05-17, 03:07 authored by Jacqueline LeungJacqueline Leung, Pankhurst, M, Dunlop, SA, Shannon HuskinsShannon Huskins, Dittmann, J, Eaton, ED, Palumaa, P, Sillard, R, Meng Inn ChuahMeng Inn Chuah, Adrian WestAdrian West, Chung, RS
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.

History

Publication title

Experimental Neurology: A Journal of Neuroscience Research

Volume

221

Pagination

98-106

ISSN

0014-4886

Department/School

Menzies Institute for Medical Research

Publisher

Academic Press Inc Elsevier Science

Place of publication

525 B St, Ste 1900, San Diego, USA, Ca, 92101-4495

Rights statement

The definitive version is available at http://www.sciencedirect.com

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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