Abstract: Phospholipase D1 (PLD1) plays a crucial role in cell differentiation of different cell types. However, the involvement of PLD1 in astrocytic differentiation remains uncertain. In the present study, we investigate the possible role of PLD1 and its product phosphatidic acid (PA) in astrocytic differentiation of hippocampal neural stem/progenitor cells (NSPCs) from hippocampi of embryonic day 16.5 rat embryos. We showed that overexpression of PLD1 increased the expression level of glial fibrillary acidic protein (GFAP), an astrocyte marker, and the number of GFAP-positive cells. Knockdown of PLD1 by transfection with Pld1 shRNA inhibited astrocytic differentiation. Moreover, PLD1 deletion (Pld1−/−) suppressed the level of GFAP in the mouse hippocampus. These results indicate that PLD1 plays a crucial role in regulating astrocytic differentiation in hippocampal NSPCs. Interestingly, PA itself was sufficient to promote astrocytic differentiation. PA-induced GFAP expression was decreased by inhibition of signal transducer and activation of transcription 3 (STAT3) using siRNA. Furthermore, PA-induced STAT3 activation and astrocytic differentiation were regulated by the focal adhesion kinase (FAK)/aurora kinase A (AURKA) pathway. Taken together, our findings suggest that PLD1 is an important modulator of astrocytic differentiation in hippocampal NSPCs via the FAK/AURKA/STAT3 signaling pathway.

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