{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:38:32Z","timestamp":1792201112254,"version":"4.4.0"},"reference-count":57,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of General Medical Sciences and NICHD of the National Institutes of Health","doi-asserted-by":"publisher","award":["R15 HD094326-01"],"award-info":[{"award-number":["R15 HD094326-01"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of General Medical Sciences and NICHD of the National Institutes of Health","doi-asserted-by":"publisher","award":["18CON-90815"],"award-info":[{"award-number":["18CON-90815"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001159","name":"Hawaii Community Foundation","doi-asserted-by":"publisher","award":["R15 HD094326-01"],"award-info":[{"award-number":["R15 HD094326-01"]}],"id":[{"id":"10.13039\/100001159","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001159","name":"Hawaii Community Foundation","doi-asserted-by":"publisher","award":["18CON-90815"],"award-info":[{"award-number":["18CON-90815"]}],"id":[{"id":"10.13039\/100001159","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Nuclear-factor-E2-related factor 2 (Nrf2) is a key transcription factor for the regulation of cellular responses to cellular stress and inflammation, and its expression is significantly lower after spontaneous term labor in human fetal membranes. Pathological induction of inflammation can lead to adverse pregnancy outcomes such as pre-eclampsia, preterm labor, and fetal death. As stretch forces are known to act upon the fetal membranes in utero, we aimed to ascertain the effect of stretch on Nrf2 to increase our understanding of the role of this stimulus on cells of the amnion at term. Our results indicated a significant reduction in Nrf2 expression in stretched isolated human amnion epithelial cells (hAECs) that could be rescued with sulforaphane treatment. Downregulation of Nrf2 as a result of stretch was accompanied with activation of proinflammatory nuclear factor-kB (NF-kB) and increases in LDH activity, ROS, and HMGB1. This work supports stretch as a key modulator of cellular stress and inflammation in the fetal membranes. Our results showed that the modulation of the antioxidant response pathway in the fetal membranes through Nrf2 activation may be a viable approach to improve outcomes in pregnancy.<\/jats:p>","DOI":"10.3390\/biom12060766","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T05:25:42Z","timestamp":1653974742000},"page":"766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Stretch Causes Cell Stress and the Downregulation of Nrf2 in Primary Amnion Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Justin Gary","family":"Padron","sequence":"first","affiliation":[{"name":"Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine, University of Hawai\u2018i at M\u0101noa, Honolulu, HI 96822, USA"},{"name":"Wayne State School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nainoa D.","family":"Norman Ing","sequence":"additional","affiliation":[{"name":"Natural Science and Mathematics, Chaminade University of Honolulu, Honolulu, HI 96816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po\u2019okela K.","family":"Ng","sequence":"additional","affiliation":[{"name":"Natural Science and Mathematics, Chaminade University of Honolulu, Honolulu, HI 96816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire E.","family":"Kendal-Wright","sequence":"additional","affiliation":[{"name":"Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine, University of Hawai\u2018i at M\u0101noa, Honolulu, HI 96822, USA"},{"name":"Natural Science and Mathematics, Chaminade University of Honolulu, Honolulu, HI 96816, USA"},{"name":"Obstetrics, Gynecology and Women\u2019s Health, John A. Burns School of Medicine, University of Hawai\u2018i at M\u0101noa, Honolulu, HI 96826, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,31]]},"reference":[{"key":"ref_1","unstructured":"(2022, May 10). 2021 MARCH OF DIMES REPORT CARD; March of Dimes. Available online: https:\/\/www.marchofdimes.org\/mission\/reportcard.aspx?gclid=Cj0KCQjw1tGUBhDXARIsAIJx01khMBvioYz-XSmFM-vdM1GzftTl5yFjTtdJh25dwmFD62-vA-eMJskaApbKEALw_wcB."},{"key":"ref_2","unstructured":"(2022, May 10). 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