{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T05:28:04Z","timestamp":1774243684759,"version":"3.50.1"},"reference-count":53,"publisher":"The Company of Biologists","issue":"19","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL119846"],"award-info":[{"award-number":["HL119846"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Placentas from pregnancies complicated by severe early-onset fetal growth restriction (FGR) exhibit diminished vascular development mediated by impaired angiogenesis, but underlying mechanisms remain unknown. In this study, we show that FGR endothelial cells demonstrate inherently reduced migratory capacity despite the presence of fibronectin, a matrix protein abundant in placental stroma that displays abnormal organization in FGR placentas. Thus, we hypothesized that aberrant endothelial-fibronectin interactions in FGR are a key mechanism underlying impaired FGR endothelial migration. Using human fetoplacental endothelial cells isolated from uncomplicated term control and FGR pregnancies, we assessed integrin \u03b15\u03b21 and \u03b1v\u03b23 regulation during cell migration. We show that endothelial integrin \u03b15\u03b21 and \u03b1v\u03b23 interactions with fibronectin are required for migration and that FGR endothelial cells responded differentially to integrin inhibition, indicating integrin dysregulation in FGR. Whole-cell expression was not different between groups. However, there were significantly more integrins in focal adhesions and reduced intracellular trafficking in FGR. These newly identified changes in FGR endothelial cellular processes represent previously unidentified mechanisms contributing to persistent angiogenic deficiencies in FGR.<\/jats:p>","DOI":"10.1242\/dev.200717","type":"journal-article","created":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T09:30:39Z","timestamp":1664875839000},"source":"Crossref","is-referenced-by-count":9,"title":["Dysregulation of integrin \u03b1v\u03b23 and \u03b15\u03b21 impedes migration of placental endothelial cells in fetal growth restriction"],"prefix":"10.1242","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9408-9701","authenticated-orcid":false,"given":"Diane L.","family":"Gumina","sequence":"first","affiliation":[{"name":"University of Colorado School of Medicine 1 Division of Reproductive Sciences, Department of Obstetrics and Gynecology , , Aurora, CO 80045 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3992-656X","authenticated-orcid":false,"given":"Shuhan","family":"Ji","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine 1 Division of Reproductive Sciences, Department of Obstetrics and Gynecology , , Aurora, CO 80045 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Flockton","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine 1 Division of Reproductive Sciences, Department of Obstetrics and Gynecology , , Aurora, CO 80045 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2942-0423","authenticated-orcid":false,"given":"Kathryn","family":"McPeak","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine 1 Division of Reproductive Sciences, Department of Obstetrics and Gynecology , , Aurora, CO 80045 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7166-8759","authenticated-orcid":false,"given":"Dominik","family":"Stich","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine 2 Department of Pharmacology , , Aurora, CO 80045 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radu","family":"Moldovan","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine 2 Department of Pharmacology , , Aurora, CO 80045 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3739-9396","authenticated-orcid":false,"given":"Emily J.","family":"Su","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine 1 Division of Reproductive Sciences, Department of Obstetrics and Gynecology , , Aurora, CO 80045 , USA"},{"name":"University of Colorado School of Medicine 3 Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology , , Aurora, CO 80045 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2022,10,4]]},"reference":[{"key":"2022100409303125400_DEV200717C1","doi-asserted-by":"publisher","first-page":"e150","DOI":"10.1097\/AOG.0000000000002046","article-title":"Committee Opinion No 700","volume":"129","author":"ACOG Committee on Practice Bulletins\u2014Obstetrics","year":"2017","journal-title":"Obstet. 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