MCP-1 involvement in glial differentiation of neuroprogenitor cells through APP signaling

    Authors

    E. G. Vrotsos; P. E. Kolattukudy;K. Sugaya

    Comments

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    Abbreviated Journal Title

    Brain Res. Bull.

    Keywords

    Amyloid precursor protein; Monocyte chemoattractant protein 1; Glial; differentiation; Astrocyte; Neuroprogenitor; AMYLOID PRECURSOR PROTEIN; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; CHEMOKINE RECEPTORS; TRANSGENIC MICE; EXPRESSION; ASTROCYTES; APOPTOSIS; CNS; Neurosciences

    Abstract

    Previously it has been reported that neural stem cells undergoing apoptotic stress have increased levels of amyloid precursor protein (APP) and increased APP expression results in glial differentiation. APP activity was also shown to be required for staurosporine-induced glial differentiation of neuroprogenitor cells. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that is expressed early during inflammation. The binding of MCPA to its chemokine receptor induces expression of novel transcription factor MCP-1-induced protein (MCPIP). MCPIP expression subsequently leads to cell death. Previous studies have shown that pro-apoptotic factors have the ability to induce neural differentiation. Therefore, we investigated if MCPIP expression leads to differentiation of NT2 neuroprogenitor cells. Results showed that MCPIP expression increased glial fibrillary acid protein (GFAP) expression and also caused distinct morphological changes, both indicative of glial differentiation. Similar results were observed with MCP-1 treatment. Interestingly, APP expression decreased in response to MCPIP. Instead, we found APP activity regulates expression of both MCP-1 and MCPIP. Furthermore, inhibition of either p38 MAPK or JAK signaling pathways significantly reduced APP's effect on MCP-1 and MCPIP. These data demonstrates the role APP has in glial differentiation of NT2 cells through MCP-1/MCPIP signaling. It is possible that increased APP expression after CNS injury could play a role in MCP-1 production, possibly promoting astrocyte activation at injured site. Published by Elsevier Inc.

    Journal Title

    Brain Research Bulletin

    Volume

    79

    Issue/Number

    2

    Publication Date

    1-1-2009

    Document Type

    Article

    Language

    English

    First Page

    97

    Last Page

    103

    WOS Identifier

    WOS:000265338700002

    ISSN

    0361-9230

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