Gene expression profiles of HTR8-S/Vneo cells after changes in ABCA1 expression.

ABCA1 is expressed in placental trophoblasts, such that when the expression level of ABCA1 changes, the function of trophoblasts dramatically changes. However, the mechanism by which ABCA1 affects the function of trophoblast cells remains unclear. Here, we used biochemical and transcriptomic to uncover the potential mechanism of the effect of ABCA1 on trophoblast function. HTR8/SVneo cells were either treated with the agonist T0901317 or transfected with siRNA to regulate ABCA1 expression levels. A human gene expression microarray was used to analyze the expression spectrum of ABCA1. Microarray results were confirmed by Western blotting and RT-PCR. Immunofluorescence allowed detection of the cellular localization of ABCA1, CCL8, CXCL10, CXCL11, and S1PR1 in HTR8/SVneo cells. Co-immunoprecipitation was used to test interactions among these proteins. Concomitant with an increase in ABCA1 expression, S1PR1 expression increased, whereas expression of CCL8, CXCL10, and CXCL11 decreased significantly; opposite effects were observed with a decrease in ABCA1 expression. Thus, changes in ABCA1 expression may lead to changes in downstream gene expression. Whereas the interaction between ABCA1 and S1PR1 was direct, interactions among ABCA1 and CCL8, CXCL10, and CXCL11 were indirect. We propose that, in conjunction with S1PR1, ABCA1 regulates expression levels of CCL8, CXCL10, and CXCL11; this may lead to changes in the immune function of trophoblastic cells. Thus, we suspect that the effect of ABCA1 on trophoblast function may involve many biological processes, molecular function changes, and the activation of multiple signaling pathways.