{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T11:05:44Z","timestamp":1772190344104,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:00:00Z","timestamp":1711411200000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Premature birth (PTB) remains a major global health concern due to its association with neonatal morbidity and mortality. The unfolded protein response (UPR) within the endoplasmic reticulum (ER) is tightly regulated by Inositol\u2010requiring enzyme type 1\u00a0(IRE\u20101), a pivotal cellular modulator. This study seeks to elucidate the role of the ER stress (ERS)\u2010related IRE\u20101 pathway in PTB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human placental trophoblast cells HTR8\/Svneo were exposed to the ER\u2010stress inducer tunicamycin (TM). The expression of IRE\u20101 and ERS\u2010associated proteins ATF6, GRP78, and XBP\u20101 was assessed in placental tissues and TM\u2010treated cells. Cellular viability, migration, invasion, and apoptosis were evaluated through a series of experimental assays. Additionally, various methods were employed to assess and verify the activation of autophagy, using the autophagy marker, microtubule\u2010associated protein 1A\/1B\u2010light chain 3 (LC3). Additionally, TUDCA (an ERS inhibitor) was used to assess its potential to counteract the TM\u2010induced cell effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Elevated levels of ATF6, GRP78, and XBP\u20101 were observed in PTB tissues and cells. TM treatment substantially reduced cell viability, migration, and invasion while promoting apoptosis. Treatment with TUDCA (an ERS inhibitor) counteracted the effects of TM on the cells. Furthermore, we identified an overexpression of IRE\u20101 in PTB tissues and cells and its knockdown enhanced cell viability, migration, and invasion while suppressed apoptosis and autophagy under TM stimulation. Notably, IRE\u20101 was found to modulate the activity of the IRE\u20101\/XBP1\/CHOP signaling pathway in TM\u2010treated cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The upregulation of IRE\u20101 in PTB placental tissues is implicated in the pathogenesis of PTB. Importantly, inhibiting the ERS\u2010associated IRE\u20101\/XBP1\/CHOP pathway may be a good strategy in mitigating PTB.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13826","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T03:53:46Z","timestamp":1711511626000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Inhibition of the endoplasmic reticulum stress\u2010associated IRE\u20101 pathway alleviates preterm birth"],"prefix":"10.1111","volume":"91","author":[{"given":"Liyin","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Obstetrics Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics &amp; Gynecology and Pediatrics Fujian Medical University  Fuzhou Fujian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Histology and 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