Title

Mcp-1 Involvement In Glial Differentiation Of Neuroprogenitor Cells Through App Signaling

Keywords

Amyloid precursor protein; Astrocyte; Glial differentiation; Monocyte chemoattractant protein 1; Neuroprogenitor

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 MCP-1 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.

Publication Date

4-29-2009

Publication Title

Brain Research Bulletin

Volume

79

Issue

2

Number of Pages

97-103

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.brainresbull.2009.01.004

Socpus ID

62349092679 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/62349092679

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