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17 September 2020 : Laboratory Research

Cyclin G2 Is Involved in the Proliferation of Placental Trophoblast Cells and Their Interactions with Endothelial Cells

Manni Sun1A, Shenghuan Liu1C, Jinlan Gao1C, Tao Meng2BC, Xuesha Xing1CD, Chen Chen1CD, Haiying Chen2E, Yang Luo1AB*

DOI: 10.12659/MSM.926414

Med Sci Monit 2020; 26:e926414

Abstract

BACKGROUND: Remodeling of maternal spiral arteries after embryo implantation relies on well-regulated trophoblast functions. Although cyclin G2 (CCNG2) is thought to be involved in placental development and function, its role in trophoblasts and the mechanisms underlying placental development and function remain unclear. The present study investigated the potential role of CCNG2 in trophoblast cell proliferation and their interactions with endothelial cells.

MATERIAL AND METHODS: CCNG2 levels were modified by stable infection of HTR8/SVneo cells with lentiviruses overexpressing and silencing CCNG2. Cell proliferation was measured using CCK-8 assays. Network formation assays were performed using trophoblasts alone and co-cultured trophoblasts and endothelial cells to measure angiogenesis of trophoblasts and trophoblast-endothelial interactions. Levels of angiogenic factors (VEGF and sFlt-1) in the supernatant were measured by ELISA, and the expression of cell cycle regulatory (cyclin D1) and invasive (MMP2, MMP3, MMP9) markers implicated in artery remodeling were measured by western blotting.

RESULTS: Ectopic expression of CCNG2 blocked the proliferation of HTR8/SVneo cells, as well as their abilities to form networks and integrate into human umbilical vein endothelial cells, whereas CCNG2 inhibition had the opposite effects. CCNG2 upregulation significantly reduced the expression of VEGF, cyclin D1, MMP2, MMP3, and MMP9, but enhanced the expression of sFlt-1. In contrast, CCNG2 downregulation had the opposite effects.

CONCLUSIONS: CCNG2 plays a critical role in trophoblast proliferation and trophoblast-endothelial cell interactions by significant affecting cell cycle, angiogenic, and invasive markers. CCNG2 may thus be a novel marker for the treatment of placental disorders.

Keywords: Cyclin G2, gestational trophoblastic disease

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750