Downstream targets of the homeobox gene DLX3 are differentially expressed in the placentae of pregnancies affected by human idiopathic fetal growth restriction

作者：Chui Amy; Kalionis Bill; Abumaree Mohamed; Cocquebert Melanie; Fournier Thierry; Evain Brion Daniele; Brennecke Shaun P; Murthi Padma^*

来源：Molecular and Cellular Endocrinology, 2013, 377(1-2): 75-83.

DOI：10.1016/j.mce.2013.06.032

• Homeobox genes
• Human placenta
• Trophoblast
• Fetal growth

Human idiopathic fetal growth restriction (FGR) is associated with placental insufficiency. Previously, we reported that the expression of homeobox gene Distal-less 3 (DLX3) is increased in idiopathic FGR placentae and is a regulator of villous trophoblast differentiation. Here, we identify the downstream targets of DIX3 in trophoblast-derived cell lines. We modelled the high levels of DLX3 in FGR using an over-expression plasmid construct and complemented this using short-interference RNA (siRNA) for inactivation in cultured cells. Using a real-time PCR-based gene profiling, candidate target genes of DLX3 over-expression and inactivation were identified as regulators of trophoblast differentiation; GATA2 and PPAR gamma. The expression of GATA2 and PPAR gamma were further assessed in placental tissues and showed increased mRNA and protein levels in FGR-affected tissues compared with gestation-matched controls. We conclude that DLX3 orchestrates the expression of multiple regulators of trophoblast differentiation and that expression of these regulatory genes is abnormal in FGR.

• 出版日期2013-9-5