PMID- 19185603 OWN - NLM STAT- MEDLINE DCOM- 20090428 LR - 20211020 IS - 1873-2747 (Electronic) IS - 0361-9230 (Print) IS - 0361-9230 (Linking) VI - 79 IP - 2 DP - 2009 Apr 29 TI - MCP-1 involvement in glial differentiation of neuroprogenitor cells through APP signaling. PG - 97-103 LID - 10.1016/j.brainresbull.2009.01.004 [doi] AB - 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. FAU - Vrotsos, Emmanuel George AU - Vrotsos EG AD - Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816-2364, USA. FAU - Kolattukudy, Pappachan E AU - Kolattukudy PE FAU - Sugaya, Kiminobu AU - Sugaya K LA - eng GR - R01 AG023472/AG/NIA NIH HHS/United States GR - R01 AG023472-01/AG/NIA NIH HHS/United States GR - AG 23472/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20090129 PL - United States TA - Brain Res Bull JT - Brain research bulletin JID - 7605818 RN - 0 (APP protein, human) RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Protease Nexins) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Cell Surface) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT3 protein, human) RN - 0 (Transcription Factors) RN - EC 2.7.10.2 (Janus Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.1.- (Ribonucleases) RN - EC 3.1.- (ZC3H12A protein, human) SB - IM MH - Amyloid beta-Protein Precursor/*metabolism MH - Cell Death/physiology MH - *Cell Differentiation/physiology MH - Cell Line MH - Chemokine CCL2/*metabolism MH - Glial Fibrillary Acidic Protein/metabolism MH - Humans MH - Janus Kinases/metabolism MH - MAP Kinase Signaling System MH - Neuroglia/cytology/*physiology MH - Phosphorylation MH - Protease Nexins MH - RNA, Messenger/metabolism MH - Receptors, Cell Surface/*metabolism MH - Ribonucleases MH - STAT3 Transcription Factor/metabolism MH - Signal Transduction MH - Stem Cells/*physiology MH - Transcription Factors/*metabolism MH - p38 Mitogen-Activated Protein Kinases/metabolism PMC - PMC3427747 MID - NIHMS108042 EDAT- 2009/02/03 09:00 MHDA- 2009/04/29 09:00 PMCR- 2012/08/26 CRDT- 2009/02/03 09:00 PHST- 2008/08/13 00:00 [received] PHST- 2008/12/17 00:00 [revised] PHST- 2009/01/06 00:00 [accepted] PHST- 2009/02/03 09:00 [entrez] PHST- 2009/02/03 09:00 [pubmed] PHST- 2009/04/29 09:00 [medline] PHST- 2012/08/26 00:00 [pmc-release] AID - S0361-9230(09)00014-8 [pii] AID - 10.1016/j.brainresbull.2009.01.004 [doi] PST - ppublish SO - Brain Res Bull. 2009 Apr 29;79(2):97-103. doi: 10.1016/j.brainresbull.2009.01.004. Epub 2009 Jan 29.