{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ginocchio S"],"funding":["NIH HHS"],"pagination":["11179"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12653012"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(22)"],"pubmed_abstract":["An underdeveloped placental vasculature is a cardinal feature in severe, early-onset fetal growth restriction with absent/reversed umbilical artery Doppler end-diastolic velocities (FGR<sub>a/r</sub>). Tissue microenvironment is a key mediator of angiogenesis; yet, the role of placental villous stromal extracellular matrix (ECM) in FGR<sub>a/r</sub> remains unknown. We applied an ECM-optimized, proteomic workflow to villous tissue and placental fibroblast cell-derived matrices (CDM) from FGR<sub>a/r</sub>, 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 FGR<sub>a/r</sub> placentas. FGR<sub>a/r</sub> 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 FGR<sub>a/r</sub> CDM, suggesting excessive deposition and crosslinking. In contrast, regulators of ECM remodeling and TGFβ 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."],"journal":["International journal of molecular sciences"],"pubmed_title":["Unraveling the Matrix: Proteomic Profiling Reveals Stromal ECM Dysregulation in Severe Early-Onset Fetal Growth Restriction."],"pmcid":["PMC12653012"],"funding_grant_id":["5R01HL119846-09"],"pubmed_authors":["Ji S","Ginocchio S","Su EJ","Gumina DL","McCabe MC","Hansen KC","Flockton AR"],"additional_accession":[]},"is_claimable":false,"name":"Unraveling the Matrix: Proteomic Profiling Reveals Stromal ECM Dysregulation in Severe Early-Onset Fetal Growth Restriction.","description":"An underdeveloped placental vasculature is a cardinal feature in severe, early-onset fetal growth restriction with absent/reversed umbilical artery Doppler end-diastolic velocities (FGR<sub>a/r</sub>). Tissue microenvironment is a key mediator of angiogenesis; yet, the role of placental villous stromal extracellular matrix (ECM) in FGR<sub>a/r</sub> remains unknown. We applied an ECM-optimized, proteomic workflow to villous tissue and placental fibroblast cell-derived matrices (CDM) from FGR<sub>a/r</sub>, 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 FGR<sub>a/r</sub> placentas. FGR<sub>a/r</sub> 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 FGR<sub>a/r</sub> CDM, suggesting excessive deposition and crosslinking. In contrast, regulators of ECM remodeling and TGFβ 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.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-05-20T03:16:01.421Z","creation":"2026-05-20T03:08:50.578Z"},"accession":"S-EPMC12653012","cross_references":{"pubmed":["41303659"],"doi":["10.3390/ijms262211179"]}}