{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:22:45Z","timestamp":1780503765935,"version":"3.54.1"},"reference-count":70,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,26]],"date-time":"2022-12-26T00:00:00Z","timestamp":1672012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171679"],"award-info":[{"award-number":["82171679"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171664"],"award-info":[{"award-number":["82171664"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2022NSCQ-MSX5209"],"award-info":[{"award-number":["2022NSCQ-MSX5209"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["wzstc-kw2022003"],"award-info":[{"award-number":["wzstc-kw2022003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chongqing Science and Technology Commission","award":["82171679"],"award-info":[{"award-number":["82171679"]}]},{"name":"Chongqing Science and Technology Commission","award":["82171664"],"award-info":[{"award-number":["82171664"]}]},{"name":"Chongqing Science and Technology Commission","award":["2022NSCQ-MSX5209"],"award-info":[{"award-number":["2022NSCQ-MSX5209"]}]},{"name":"Chongqing Science and Technology Commission","award":["wzstc-kw2022003"],"award-info":[{"award-number":["wzstc-kw2022003"]}]},{"name":"Wanzhou Science and Technology Commission","award":["82171679"],"award-info":[{"award-number":["82171679"]}]},{"name":"Wanzhou Science and Technology Commission","award":["82171664"],"award-info":[{"award-number":["82171664"]}]},{"name":"Wanzhou Science and Technology Commission","award":["2022NSCQ-MSX5209"],"award-info":[{"award-number":["2022NSCQ-MSX5209"]}]},{"name":"Wanzhou Science and Technology Commission","award":["wzstc-kw2022003"],"award-info":[{"award-number":["wzstc-kw2022003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Preeclampsia is a leading contributor to increased maternal morbidity and mortality in the perinatal period. Increasing evidence demonstrates that ferroptosis is an essential mechanism for the pathogenesis of preeclampsia. Elabela is a novel small-molecule polypeptide, mainly expressed in embryonic and transplacental tissues, with an ability to promote cell proliferation and invasion. However, its specific regulatory mechanism in preeclampsia has not been completely elucidated. In this study, we first reveal an increased grade of ferroptosis accompanied by a downregulation of the expression of Elabela in preeclampsia placentas. We then confirm the presence of a ferroptosis phenotype in the placenta of the mouse PE-like model, and Elabela can reduce ferroptosis in the placenta and improve adverse pregnancy outcomes. Furthermore, we demonstrate that targeting Elabela alleviates the cellular dysfunction mediated by Erastin promoting increased lipid peroxidation in vitro. Subsequent mechanistic studies suggest that Elabela increases FTH1 levels by inhibiting the ferritinophagy pathway, and consequently chelates the intracellular labile iron pool and eventually arrests ferroptosis. In conclusion, Elabela deficiency exacerbates ferroptosis in the placenta, which is among the potential mechanisms in the pathogenesis of preeclampsia. Targeting the Elabela\u2013ferritinophagy\u2013ferroptosis signaling axis provides a new therapeutic intervention strategy to alleviate preeclampsia.<\/jats:p>","DOI":"10.3390\/cells12010099","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T07:31:56Z","timestamp":1672126316000},"page":"99","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Elabela: Negative Regulation of Ferroptosis in Trophoblasts via the Ferritinophagy Pathway Implicated in the Pathogenesis of Preeclampsia"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8308-4400","authenticated-orcid":false,"given":"Huan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Chongqing University Three Gorges Hospital, Chongqing 404100, China"},{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University, Chongqing 400016, China"},{"name":"Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubin","family":"Ding","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University, Chongqing 400016, China"},{"name":"Department of Obstetrics and Gynecology, Women and Children\u2019s Hospital of Chongqing Medical University, Chongqing 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Chongqing University Three Gorges Hospital, Chongqing 404100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojian","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Chongqing University Three Gorges Hospital, Chongqing 404100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University, Chongqing 400016, China"},{"name":"Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency, Chongqing University Three Gorges Hospital, Chongqing 404100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University, Chongqing 400016, China"},{"name":"Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2577-9247","authenticated-orcid":false,"given":"Jie","family":"He","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University, Chongqing 400016, China"},{"name":"Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelan","family":"Tao","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University, Chongqing 400016, China"},{"name":"Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Chongqing University Three Gorges Hospital, Chongqing 404100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Qi","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University, Chongqing 400016, China"},{"name":"Department of Obstetrics and Gynecology, Women and Children\u2019s Hospital of Chongqing Medical University, Chongqing 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"FIGO Working Group on Good Clinical Practice in Maternal\u2014Fetal Medicine, Di Renzo, G.C., Fonseca, E., Gratacos, E., Hassan, S., Kurtser, M., Malone, F., Nambiar, S., Nicolaides, K., and Sierra, N. 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