Impact of the Immunomodulatory Factor Soluble B7-H4 in the Progress of Preeclampsia by Inhibiting Essential Functions of Extravillous Trophoblast Cells.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Pre-Eclampsia*/pathology ; Pre-Eclampsia*/metabolism ; Trophoblasts*/metabolism ; Trophoblasts*/pathology ; V-Set Domain-Containing T-Cell Activation Inhibitor 1*/metabolism ; Cell Movement* ; Cell Proliferation* ; Signal Transduction*; Humans ; Female ; Pregnancy ; Apoptosis ; Cell Line ; Proto-Oncogene Proteins c-akt/metabolism ; Immunologic Factors/metabolism ; STAT3 Transcription Factor/metabolism ; Placenta/metabolism ; Adult ; Phosphatidylinositol 3-Kinases/metabolism ; Extravillous Trophoblasts

A key aspect of preeclampsia pathophysiology is the reduced invasiveness of trophoblasts and the impairment of spiral artery remodelling. Understanding the causes of altered trophoblast function is critical to understand the development of preeclampsia. B7-H4, a checkpoint molecule, controls a wide range of processes, including T-cell activation, cytokine release, and tumour progression. Our previous findings indicated that B7-H4 levels are elevated in both maternal blood and placental villous tissue during the early stages of preeclampsia. Here, we investigated the function of B7-H4 in trophoblast physiology. Recombinant B7-H4 protein was used to treat human SGHPL-5 extravillous trophoblast cells. Biological functions were investigated using MTT, wound healing, and transwell assays. Signalling pathways were analysed by immunoblotting and immunofluorescence. The functionality of B7-H4 was further confirmed by immunoblotting and immunohistochemical analysis in placental tissues from control and preeclamptic patients following therapeutic plasma exchange (TPE) or standard of care treatment. This study showed that B7-H4 inhibited the proliferation, migration, and invasion capacities of SGHPL-5 extravillous cells while promoting apoptosis by downregulating the PI3K/Akt/STAT3 signalling pathway. These results were consistently confirmed in placental tissues from preterm controls compared to early-onset preeclamptic placental tissues from patients treated with standard of care or TPE treatment. B7-H4 may play a role in the development of preeclampsia by inhibiting essential functions of extravillous trophoblast cells during placental development. One possible mechanism by which TPE improves pregnancy outcomes in preeclampsia is through the elimination of B7-H4 amongst other factors.

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491780329 Deutsche Forschungsgemeinschaft

Keywords: Akt; B7-H4; STAT3; placenta; preeclampsia; trophoblast

0 (V-Set Domain-Containing T-Cell Activation Inhibitor 1)
0 (VTCN1 protein, human)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
0 (Immunologic Factors)
0 (STAT3 Transcription Factor)
EC 2.7.1.- (Phosphatidylinositol 3-Kinases)

Date Created: 20240828 Date Completed: 20240828 Latest Revision: 20240830

20250114

PMC11352994

10.3390/cells13161372

39195262