当前位置： SCI文献检索 > NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY期刊下所有文献 > STAT3 represents a molecular switch possibly inducing astroglial instead of oligodendroglial differentiation of oligodendroglial progenitor cells in Theiler's murine encephalomyelitis.

STAT3 represents a molecular switch possibly inducing astroglial instead of oligodendroglial differentiation of oligodendroglial progenitor cells in Theiler's murine encephalomyelitis.

Abstract：

AIMS:Insufficient oligodendroglial differentiation of oligodendroglial progenitor cells (OPCs) is suggested to be responsible for remyelination failure and astroglial scar formation in Theiler's murine encephalomyelitis (TME). The aim of the present study is to identify molecular key regulators of OPC differentiation in TME, and to dissect their mechanism of action in vitro. METHODS:TME virus (TMEV) infected SJL/J-mice were evaluated by rotarod analysis, histopathology, immunohistology and gene expression microarray analysis. The STAT3 pathway was activated using meteorin and inhibited using STAT3 inhibitor VII in the glial progenitor cell line BO-1 and in primary rat OPCs in vitro. RESULTS:As expected, immunohistology demonstrated progressively decreasing myelin basic protein-positive white matter in TME. In contrast, intralesional NG2-positive OPCs as well as GFAP-positive astrocytes were increased. Gene Set Enrichment Analysis revealed 26 Gene Ontology terms including 'JAK-STAT cascade' to be significantly positively correlated with the density of NG2-positive OPCs. Immunohistology revealed an increased amount of activated, phosphorylated STAT3-expressing astrocytes, OPCs, and microglia/macrophages within the lesions. Meteorin-induced activation of STAT3-signalling in BO-1 cells and primary rat OPCs resulted in an enhanced GFAP and reduced CNPase expression. In contrast, an oppositional result was observed in BO-1 cells treated with STAT3 inhibitor VII. CONCLUSIONS:The STAT3 pathway is a key regulator of OPC-differentiation, suggested to shift their differentiation from an oligodendroglial towards an astrocytic fate, thereby inducing astrogliosis and insufficient remyelination in TME.

journal_name

Neuropathol Appl Neurobiol

journal_title

Neuropathology and applied neurobiology

authors

Sun Y,Lehmbecker A,Kalkuhl A,Deschl U,Sun W,Rohn K,Tzvetanova ID,Nave KA,Baumgärtner W,Ulrich R

doi

10.1111/nan.12133

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

347-70

issue

eissn

0305-1846

issn

1365-2990

journal_volume

pub_type

杂志文章

在线工具

STAT3 represents a molecular switch possibly inducing astroglial instead of oligodendroglial differentiation of oligodendroglial progenitor cells in Theiler's murine encephalomyelitis.