{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:18:36Z","timestamp":1790702316198,"version":"4.1.0"},"reference-count":163,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T00:00:00Z","timestamp":1685836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Placentation is a key and tightly regulated process that ensures the normal development of the placenta and fetal growth. Preeclampsia (PE) is a hypertensive pregnancy-related disorder involving about 5\u20138% of all pregnancies and clinically characterized by de novo maternal hypertension and proteinuria. In addition, PE pregnancies are also characterized by increased oxidative stress and inflammation. The NRF2\/KEAP1 signaling pathway plays an important role in protecting cells against oxidative damage due to increased reactive oxygen species (ROS) levels. ROS activate NRF2, allowing its binding to the antioxidant response element (ARE) region present in the promoter of several antioxidant genes such as heme oxygenase, catalase, glutathione peroxidase and superoxide dismutase that neutralize ROS, protecting cells against oxidative stress damages. In this review, we analyze the current literature regarding the role of the NRF2\/KEAP1 pathway in preeclamptic pregnancies, discussing the main cellular modulators of this pathway. Moreover, we also discuss the main natural and synthetic compounds that can regulate this pathway in in vivo and in vitro models.<\/jats:p>","DOI":"10.3390\/cells12111545","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T01:53:25Z","timestamp":1685930005000},"page":"1545","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":123,"title":["Modulation of NRF2\/KEAP1 Signaling in Preeclampsia"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7003-1230","authenticated-orcid":false,"given":"Giovanni","family":"Tossetta","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5630-5984","authenticated-orcid":false,"given":"Sonia","family":"Fantone","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3338-1172","authenticated-orcid":false,"given":"Federica","family":"Piani","sequence":"additional","affiliation":[{"name":"Cardiovascular Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40128 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Crescimanno","sequence":"additional","affiliation":[{"name":"School of Human and Social Science, University \u201cKore\u201d of Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ciavattini","sequence":"additional","affiliation":[{"name":"Clinic of Obstetrics and Gynaecology, Department of Clinical Sciences, Universit\u00e0 Politecnica delle Marche, Salesi Hospital, 60123 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9427-1391","authenticated-orcid":false,"given":"Stefano Raffaele","family":"Giannubilo","sequence":"additional","affiliation":[{"name":"Clinic of Obstetrics and Gynaecology, Department of Clinical Sciences, Universit\u00e0 Politecnica delle Marche, Salesi Hospital, 60123 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Marzioni","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.rbmo.2015.10.005","article-title":"The endocrine function of human placenta: An overview","volume":"32","author":"Costa","year":"2016","journal-title":"Reprod. 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