{"doi":"10.3390/ijms262211179","title":"Unraveling the Matrix: Proteomic Profiling Reveals Stromal ECM Dysregulation in Severe Early-Onset Fetal Growth Restriction","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 (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 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","year":2025,"id":537217,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":252044,"name":"Maxwell C. McCabe","orcid":"0000-0002-3599-694X","position":1,"is_corresponding":false},{"id":561366,"name":"Amanda Flockton","orcid":null,"position":2,"is_corresponding":false},{"id":945359,"name":"Diane L. Gumina","orcid":"0000-0001-9408-9701","position":3,"is_corresponding":false},{"id":11001,"name":"Kirk C. Hansen","orcid":"0000-0001-5054-838X","position":4,"is_corresponding":false},{"id":945360,"name":"Shuhan Ji","orcid":"0000-0002-3992-656X","position":5,"is_corresponding":false},{"id":839246,"name":"Emily Su","orcid":"0000-0003-3739-9396","position":6,"is_corresponding":false},{"id":1423023,"name":"S. Ginocchio","orcid":"0000-0003-0952-6212","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-19T02:52:12.997494Z","pmid":"41303659","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}