A novel peptide promotes human trophoblast proliferation and migration through PI3K/Akt/mTOR signaling pathway

Abstract

Background: Preeclampsia (PE) is a complex pregnancy-related disease that endangers the safety of maternal and fetal. The purpose of this study is to reveal the pathogenesis of preeclampsia and discover new predictors from the perspective of peptidomics. The umbilical cord blood of PE and control group was analyzed by peptidomics. A peptide named Regulation of Proliferation Process in Preeclampsia (ROPPIP) was screened out to explore its role in the proliferation, migration and apoptosis of trophoblast cells in preeclampsia. Methods: We compared and analyzed the umbilical cord blood of patients with PE and normal pregnant women using liquid chromatography-tandem mass spectrometry (LC-MS). hTR-8/Svneo cells cultured in vitro were divided into ROPPIP group and a disordered peptide group as control. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, Transwell chamber assays and western blot analysis were performed to detect cell proliferation, invasion, migration and apoptosis, in addition to the expression of Matrix metalloproteinase-2 (MMP2), nuclear associated antigen Ki67, B-cell lymphoma-2 (Bcl2), Caspase 3, and β-actin protein. Results: We identified 133 differential peptides. Of these, 51 were up-regulated while 82 were downregulated. the polypeptide SFGVRMATASPTDGNV with low differential expression in the serum of PE patients was selected for the study, we named the polypeptide as Regulation of Proliferation Process in PE (ROPPIP). The experiment shows that ROPPIP can up-regulate the expression levels of MMP2, Ki67, and Bcl2 in HTR-8/Svneo cells, down-regulate the expression of caspase-3, promote the proliferation and migration of HTR-8/Svneo cells and inhibit the apoptosis induced by cisplatin, the activation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway may be associated with the function of ROPPIP. Conclusions: ROPPIP promotes HTR-8/Svneo cells migration and proliferation, and inhibits apoptosis, by regulating the activation of the PI3K/AKT/mTOR signaling pathway.

SNHG22 promotes migration and invasion of trophoblasts via miR-128-3p/PCDH11X axis and activates PI3K/Akt signaling pathway

“…Interestingly, according to previous evidence, PI3K/Akt signaling pathway significantly contributed to the development of trophoblasts. 9 , 33 Herein, it was demonstrated that SNHG22 could activate PI3K/Akt signaling pathway to accelerate trophoblast migration and invasion via mediating miR-128-3p/PCDH11X. Although the authors displayed sufficient rationales to support the critical role of SNHG22 in promoting biological behaviors of trophoblasts, the authors’ findings remain to be further investigated by in vivo studies.…”

“… 7 In addition, it has been proved that trophoblast dysfunction significantly contributes to the induction of PE, 8 and increasing evidence has highlighted that normal proliferation and migration of trophoblasts can prevent PE. 9 , 10 Thus, it is necessary to identify indicators involved in the migration and invasion of trophoblasts for the prevention of PE.…”

Identification of LncRNA-miRNA-mRNA ceRNA network in hypoxia-induced HTR-8/SVneo cells for preeclampsia

“…PI3K/Akt, mTOR, and AMPK are serine/threonine kinases that play essential roles in regulating the proliferation and invasion of trophoblast cells and ameliorating placental oxidative stress in PE. [42][43][44] The Notch signaling pathway is a hypoxia-inducible pathway that is critical for placental formation, functions, and regulates trophoblast invasion. [45,46] Moreover, some of the 27 mRNAs have been reported to play essential roles in placental development.…”