MCP-1 involvement in glial differentiation of neuroprogenitor cells through APP signaling.
MCP-1 involvement in glial differentiation of neuroprogenitor cells through APP signaling.
复制标题
通过应用信号传导，MCP-1参与神经元基因细胞的神经胶质分化。
DOI：
10.1016/j.brainresbull.2009.01.004
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发表时间：
2009-04-29
影响因子：
3.8
通讯作者：
Sugaya, Kiminobu
中科院分区：
文献类型：
--
作者：
Vrotsos, Emmanuel George;Kolattukudy, Pappachan E.;Sugaya, Kiminobu
关键词：
先前已经报道，经历凋亡应激的神经干细胞具有增加的淀粉样前体蛋白（APP）水平，并且增加的APP表达导致神经胶质分化。APP活性也被证明是星形孢菌素诱导的神经祖细胞的神经胶质分化所必需的。单核细胞趋化蛋白-1（MCP-1）是一种在炎症早期表达的趋化因子。MCP-1与其趋化因子受体的结合诱导新的转录因子MCP-1诱导蛋白（MCPIP）的表达。MCPIP表达随后导致细胞死亡。以往的研究表明，促凋亡因子具有诱导神经分化的能力。因此，我们研究了MCPIP表达是否导致NT 2神经祖细胞的分化。结果表明，MCPIP表达增加胶质细胞酸性蛋白（GFAP）的表达，也引起了明显的形态学变化，都表明胶质细胞分化。用MCP-1处理观察到类似的结果。有趣的是，APP的表达减少响应MCPIP。相反，我们发现APP活性调节MCP-1和MCPIP的表达。此外，抑制p38 MAPK或JAK信号通路显著降低APP对MCP-1和MCPIP的作用。这些数据表明APP通过MCP-1/MCPIP信号传导在NT 2细胞的神经胶质分化中的作用。CNS损伤后APP表达增加可能在MCP-1的产生中起作用，可能促进损伤部位星形胶质细胞的活化。
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.
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