RhoGDI2 Is Expressed in Human Trophoblasts and Involved in Their Migration by Inhibiting the Activation of RAC11

Abstract

The invasion of placental trophoblast cells into the maternal decidua is an essential aspect of placental embedment. The process of placentation bears several striking similarities to tumor cell metastasis. However, trophoblastic migration during implantation and placentation is stringently controlled both in space and time. RhoGDI2 belongs to a family of Rho guanosine diphosphate dissociation inhibitors (RhoGDIs), and RhoGDI2 is a metastasis suppressor gene and a marker of aggressive human cancer. We evaluated whether RhoGDI2 has a physiological role in embryo implantation, particularly trophoblast migration. The mRNA and protein expression levels of RhoGDI2 were higher in term placentas compared with first-trimester placentas as detected by real-time PCR and Western blot. Immunohistochemical studies indicated that RhoGDI2 localized to the cytotrophoblast layer and extravillous trophoblast in first-trimester placentas and was distributed in the syncytiotrophoblast layers of term placentas. Overexpression of RhoGDI2 in HTR-8/SVneo cells was associated with reduced RAC1-guanosine triphosphate (GTP) levels and inhibited cell migration. Conversely, small interfering RNA-mediated downregulation of RhoGDI2 resulted in significantly increased RAC1-GTP levels. Altered RhoGDI2 expression had no significant effects on cell proliferation. In conclusion, RhoGDI2 inhibits trophoblast cell migration, and this function may involve suppression of RAC1 activation.

Rac1/β-Catenin Signalling Pathway Contributes to Trophoblast Cell Invasion by Targeting Snail and MMP9

“…Compared to normal pregnancy tissues, our research discovered that Rac1 expression declined in preeclampsia placental tissues. This evidence, along with the previous observation that Rac1 activity was significantly lower in women with preeclampsia and HELLP [6][7][8], supports the view that Rac1 potentially contributes to placental development. Furthermore, the present study showed the activity of Rac1 at different gestational stages and under preeclampsia conditions; these changes corresponded with the down-regulation of trophoblast invasion, suggesting that Rac1 may be involved in the regulation of trophoblast invasion to prevent shallow placental implantation.…”

“…Moreover, the activation of PTGER1 and PTGER4 which serve as mediators of the PGE 2 -induced migration of first trimester human EVTs can activate Rac1 [7]. A recent study indicated that RhoGDI2, which belongs to a family of Rho guanosine diphosphate dissociation inhibitors, suppressed EVT migration by inhibiting the activation of Rac1 [8]. These collective observations suggest that Rac1 may play a critical role in EVT invasion.…”

Placenta-derived extracellular vesicles: their cargo and possible functions

“…The Rho GTPases are also Ras-like proteins and are involved in several cellular functions including actin dynamics and vesicular trafficking (Bustelo et al 2007). They positively regulate trophoblast migration (Shiokawa et al 2002;Liu et al 2014) and their expression can be increased by hypoxia (Hayashi et al 2005), which may, in part, explain the significant increase in STB microvesicles in the circulation during PE (see Table 2). …”

Biomarcadores da tuberculose: uma revisão da literatura.

“…Os autores sugerem que a geração dos granulomas possa ser afetada pela regulação da matriz extracelular, com a destruição desta ocasionada pela ação da ARHGDIB, havendo aumento nos pacientes não tratados seguido da redução nos curados. No entanto essa hipótese é fundada em trabalhos que retratam o papel da ARHGDIB na perspectiva oncológica e reprodutiva (JUN CHO et al, 2014;LIU et al, 2014;YI et al, 2014), sendo interessante futuros estudos para seu entendimento em modelos específicos de TB.…”