{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T06:58:49Z","timestamp":1765609129567,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T00:00:00Z","timestamp":1723852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation (DFG)","doi-asserted-by":"publisher","award":["491780329","202108130056","201808310086"],"award-info":[{"award-number":["491780329","202108130056","201808310086"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Open Access Publication Fund of the University of Duisburg-Essen. Yuyang Ma","award":["491780329","202108130056","201808310086"],"award-info":[{"award-number":["491780329","202108130056","201808310086"]}]},{"name":"China Scholarship Council (CSC)","award":["491780329","202108130056","201808310086"],"award-info":[{"award-number":["491780329","202108130056","201808310086"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells13161372","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T03:43:28Z","timestamp":1724039008000},"page":"1372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Impact of the Immunomodulatory Factor Soluble B7-H4 in the Progress of Preeclampsia by Inhibiting Essential Functions of Extravillous Trophoblast Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Yuyang","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyan","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrix","family":"Reisch","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer","family":"Kimmig","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3982-7027","authenticated-orcid":false,"given":"Antonella","family":"Iannaccone","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9506-4581","authenticated-orcid":false,"given":"Alexandra","family":"Gellhaus","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,17]]},"reference":[{"key":"ref_1","unstructured":"Karrar, S.A., Martingano, D.J., and Hong, P.L. 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