{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T16:59:40Z","timestamp":1780333180164,"version":"3.54.1"},"reference-count":98,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"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":["R01HL119-846"],"award-info":[{"award-number":["R01HL119-846"]}],"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":["P30CA06934"],"award-info":[{"award-number":["P30CA06934"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Mass Spectrometry Proteomic Shared Resource","award":["RRID SCR_021988"],"award-info":[{"award-number":["RRID SCR_021988"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>An underdeveloped placental vasculature is a cardinal feature in severe, early-onset fetal growth restriction with absent\/reversed umbilical artery Doppler end-diastolic velocities (FGRa\/r). Tissue microenvironment is a key mediator of angiogenesis; yet, the role of placental villous stromal extracellular matrix (ECM) in FGRa\/r remains unknown. We applied an ECM-optimized, proteomic workflow to villous tissue and placental fibroblast cell-derived matrices (CDM) from FGRa\/r, gestational age-matched controls, and uncomplicated term pregnancies. No significant differences were detected in villous tissue, although there was a trend toward increased type I collagen and fibronectin in FGRa\/r placentas. FGRa\/r CDM, however, appeared distinct from both control groups, with elevated matrisome abundance, greater insolubility of matrisome-associated proteins, and 44 differentially expressed matrisome proteins. Fibronectin emerged as a central network hub among differential matrisome proteins, interacting with thrombospondin-1, vitronectin, and transglutaminase-2, all of which were enriched in FGRa\/r CDM, suggesting excessive deposition and crosslinking. In contrast, regulators of ECM remodeling and TGF\u03b2 activity, including fibrillin-1, decorin, and syndecan-4, were depleted. These features suggest a pro-fibrotic, dysregulated stroma with diminished remodeling capacity. Our findings establish the first, comprehensive proteomic map of human placental stromal matrisome and provide a molecular framework for understanding how aberrant ECM organization contributes to placental dysfunction.<\/jats:p>","DOI":"10.3390\/ijms262211179","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T11:17:27Z","timestamp":1763551047000},"page":"11179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unraveling the Matrix: Proteomic Profiling Reveals Stromal ECM Dysregulation in Severe Early-Onset Fetal Growth Restriction"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0952-6212","authenticated-orcid":false,"given":"Stefano","family":"Ginocchio","sequence":"first","affiliation":[{"name":"Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3599-694X","authenticated-orcid":false,"given":"Maxwell C.","family":"McCabe","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda R.","family":"Flockton","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane L.","family":"Gumina","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk C.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhan","family":"Ji","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3739-9396","authenticated-orcid":false,"given":"Emily J.","family":"Su","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO 80045, USA"},{"name":"Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hynes, R.O., and Naba, A. 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