Elevated PGT promotes proliferation and inhibits cell apoptosis in preeclampsia by Erk signaling pathway.

Prostaglandins participate in maternal recognition of pregnancy, implantation and maintenance of gestation. Prostaglandin transporter (PGT), as a candidate molecule of prostaglandin carriers, might be involved in the pathogenesis of preeclampsia. In preeclampsia (PE) patients' placental tissue, we identified PGT by RNA sequencing, measured its expression pattern by quantitative real-time PCR and Western blot. PGT was found to be upregulated in preeclamptic placental tissue. The expression pattern of PGT in PE was double confirmed by eight Gene Expression Omnibus (GEO) databases. In abortion tissues at 6-8 weeks, we then observed the cellular location of PGT by Immunofluorescence technique (IF) and found PGT located in trophoblast cell of the placenta of early pregnancy. In vitro studies revealed that forced expression of PGT in HTR8/Sveno cell inhibited its apoptosis, but promoted its proliferation by activating Erk signaling. In vivo study, we used reduced uterine perfusion pressure (RUPP) rat model and L-NAME-induced preeclampsia-like rats to study the possible role of PGT in preeclampsia. And PGT was found to be upregulated in both preeclampsia rat models by Immunohistochemical (IHC) staining. Newly identified PGT plays an important role in trophoblast proliferation via Erk signaling, providing new insights for understanding the pathogenesis of PE.

The Enzyme 15-Hydroxyprostaglandin Dehydrogenase Inhibits a Shift to the Mesenchymal Pattern of Trophoblasts and Decidual Stromal Cells Accompanied by Prostaglandin Transporter in Preeclampsia.

Preeclampsia (PE) is a pregnancy complication beginning after 20 weeks of pregnancy that involves high blood pressure (systolic > 140 mmHg or diastolic > 90 mmHg), with or without proteinuria. Insufficient trophoblast invasion and abnormal decidualization are involved in PE development. However, whether unhealthy placenta and decidua have the same biological activities is unclear. The enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH; encoded by HPGD) degrades prostaglandin, and prostaglandin transporter (PGT), as a candidate molecule of prostaglandin carriers, helps transport prostaglandin into cells. Whether 15-PGDH and PGT are involved in PE has not been researched. In this study, we investigated the shared pathogenesis of foetal placenta and maternal decidua from the perspective of epithelial-mesenchymal transition (EMT)/mesenchymal-epithelial transition (MET) and explored the combined effects of 15-PGDH and PGT on the EMT/MET of trophoblasts and decidual stromal cells (DSCs). Here, we demonstrated that placental development and decidualization both involved EMT/MET. In PE, both trophoblasts and DSCs show more epithelial patterns. Moreover, 15-PGDH expression was downregulated in the placentas but upregulated in the deciduas of PE patients. Inhibiting 15-PGDH promotes a shift to a mesenchymal pattern of trophoblasts and DSCs depending on the PGT-mediated transport of prostaglandin E2 (PGE2). In conclusion, our results showed that inhibiting 15-PGDH promotes a shift to the mesenchymal pattern of trophoblasts and DSCs and may provide a new and alternative therapy for the treatment of PE.

Three categories of similarities between the placenta and cancer that can aid cancer treatment: Cells, the microenvironment, and metabolites.

Cancer is one of the most harmful diseases, while pregnancy is a common condition of females. Placenta is the most important organ for fetal growth, which has not been fully understand. It's well known that placenta and solid tumor have some similar biological behaviors. What's more, decidua, the microenvironment of placenta, and metabolism all undergo adaptive shift for healthy pregnancy. Interestingly, decidua and the tumor microenvironment (TME); metabolism changes during pregnancy and cancer cachexia all have underlying links. However, whether the close link between pregnancy and cancer can bring some new ideas to treat cancer is still unclear. So, in this review we note that pregnancy may offer clues to treat cancer related to three categories: from cell perspective, through the shared development process of the placenta and cancer; from microenvironment perspective, though the shared features of the decidua and TME; and from metabolism perspective, through shared metabolites changes during pregnancy and cancer cachexia. Firstly, comparing gene mutations of both placenta and cancer, which is the underlying mechanism of many similar biological behaviors, helps us understand the origin of cancer and find the key factors to restore tumorigenesis. Secondly, exploring how decidua affect placenta development and similarities of decidua and TME is helpful to reshape TME, then to inhibit cancer. Thirdly, we also illustrate the possibility that the altered metabolites during pregnancy may reverse cancer cachexia. So, some key molecules changed in circulation of pregnancy may help relieve cachexia and make survival with cancer realized.