期刊
STEM CELLS
卷 27, 期 11, 页码 2824-2832出版社
WILEY
DOI: 10.1002/stem.225
关键词
C3a; ERK1/2 phosphorylation; Neural progenitor cells; Neuronal differentiation; Migration
资金
- Swedish Research Council [20116, 11548]
- LUA/ALF Goteborg
- Region of Vastra Gotaland (RUN)
- Ragnar and Torsten Soderberg's Foundations
- Hjarnfonden
- Edith Jacobsson's Foundation
- John and Brit Wennerstrom's Foundation for Neurological Research
- W. and M. Lundgren's Foundation
- A. and U. Amlov's Foundation
- Free Mason Foundation
- Swedish Stroke Foundation
Anaphylatoxin C3a is a third complement component (C3)-derived peptide, the multiple functions of which range from stimulation of inflammation to neuroprotection. In a previous study, we have shown that signaling through C3a receptor positively regulates in vivo neurogenesis in adult mouse brain. Here, we studied the direct effects of C3a on adult mouse whole brain-derived neural progenitor cells (NPCs) in vitro. Our results demonstrate that NPCs bind C3a in a specific and reversible manner and that C3a stimulates neuronal differentiation of NPCs. Furthermore, C3a stimulated the migration of NPCs induced by low concentrations of stromal cell-derived factor (SDF)-1 alpha, whereas it inhibited NPC migration at high concentration of SDF-1 alpha. In the same manner, C3a modulated SDF-1 alpha-induced extracellular-signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation in these cells. In addition, C3a had inhibitory effect on SDF-1 alpha-induced neuronal differentiation of NPCs. These data show that C3a modulates SDF-1 alpha-induced differentiation and migration of these cells, conceivably through the regulation of ERK1/2 phosphorylation. Our results provide the first evidence that C3a regulates neurogenesis by directly affecting the fate and properties of NPCs. STEM CELLS 2009; 27: 2824-2832
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