{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:23:05Z","timestamp":1767205385699,"version":"build-2238731810"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL049277"],"award-info":[{"award-number":["R01HL049277"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HD101485"],"award-info":[{"award-number":["R01HD101485"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Life"],"abstract":"<jats:p>In preeclampsia (PE), impaired trophoblast proliferation and differentiation are thought to cause abnormal placentation and subsequent clinical manifestations of the disease, i.e., hypertension, proteinuria, and end-organ damage. Insulin-like growth factor-1 (IGF-1) influences trophoblast cell function; however, the mechanism of IGF-1\u2019s action on trophoblasts is not understood well. Inhibitor of DNA binding protein 2 (ID2) is involved in trophoblast differentiation and implicated in many processes disrupted in PE, including placental development, vascular differentiation, and angiogenesis. We hypothesized that IGF-1 regulates trophoblast proliferation and differentiation via ID2. Immortalized human first trimester trophoblast cells (HTR-8\/SVneo) were treated with IGF-1 for 24 h after serum starvation. ID2 mRNA and protein were measured, as well as trophoblast cell viability, proliferation, tube formation, and migration. IGF-1 decreased ID2 expression in a dose-dependent manner. IGF-1 decreased trophoblast proliferation but increased cell viability, differentiation, and migration. ID2 overexpression mitigated the effects of IGF-1 on trophoblast cells. These data suggest that IGF-1 could regulate trophoblast proliferation and differentiation through ID2. The dysregulation of ID2-mediated IGF-1 signaling in trophoblast cells could be involved in the pathogenesis of pregnancy disorders like uterine growth restriction and PE.<\/jats:p>","DOI":"10.3390\/life14121663","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T06:48:39Z","timestamp":1734331719000},"page":"1663","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibitor of DNA Binding Protein 2 (ID2) Mediates the Anti-Proliferative and Pro-Differentiation Effects of Insulin-like Growth Factor-1 (IGF-1)"],"prefix":"10.3390","volume":"14","author":[{"given":"Rebecca","family":"Ssengonzi","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuye","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7301-2698","authenticated-orcid":false,"given":"Jiayi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukako","family":"Kayashima","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. H. Davin","family":"Townley-Tilson","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Balaji","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, Golden LEAF Biomanufacturing Training and Education Center, North Carolina State University, Raleigh, NC 27606, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyo","family":"Maeda-Smithies","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6779-5077","authenticated-orcid":false,"given":"Feng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3479","DOI":"10.1007\/s00018-019-03104-6","article-title":"Human placenta and trophoblast development: Key molecular mechanisms and model systems","volume":"76","author":"Haider","year":"2019","journal-title":"Cell. 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