Upregulated Fibulin-1 Increased Endometrial Stromal Cell Viability and Migration by Repressing EFEMP1-Dependent Ferroptosis in Endometriosis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35127942", "kind": "science-record", "revision": 6, "content_hash": "sha256:a3d33de92ed6eac94537ef6da967165b5c9f8eed7468d95a0eaf1e948d151362", "created_at": "2026-11-01T17:36:53Z", "updated_at": "2026-11-01T22:48:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Upregulated Fibulin-1 Increased Endometrial Stromal Cell Viability and Migration by Repressing EFEMP1-Dependent Ferroptosis in Endometriosis.", "doi": "10.1155/2022/4809415", "pmid": "35127942", "authors": ["Yiting Wan", "Yanhua Song", "Jing Chen", "Jueying Kong", "CanCan Gu", "Jiami Huang", "Ling Zuo"], "journal": "BioMed research international", "year": 2022, "abstract": "Endometriosis (EMS) is a prevalent disease in women characterized by the presence of endometrial stroma and glands outside the uterus. Recent studies have showed that EMS is correlated with the resistance of endometrial stromal cells (ESCs) to ferroptosis, an iron-dependent nonapoptotic cell death. Fibulin-1 (FBLN1) is a newly identified target regulated by progesterone in the process of ESC decidualization. However, the role of FBLN1 in regulating ESC ferroptosis and EMS remains unclear. In the present study, the gene expression profiles of GSE58178, GSE23339, and GSE25628 were downloaded from the Gene Expression Omnibus (GEO) database, and the commonly differential genes were identified using Venn diagram analysis. The role of FBLN1 in ESC viability and migration was evaluated using Cell Counting Kit-8, transwell, and western blot analysis. We found that the FBLN1 expression was increased significantly in eutopic and ectopic endometrial tissues of patients with EMS compared with normal endometrium. FBLN1 overexpression in normal ESCs (NESCs) promoted cell viability and migration, whereas FBLN1 inhibition in ectopic ESCs (EESCs) decreased cell viability and migration. Furthermore, FBLN1 inhibition facilitated EESC death by triggering ferroptosis, as evidenced by increased Fe2+, lipid ROS, and malondialdehyde (MDA) level and decreased glutathione peroxidase 4 (GPX4) expression and glutathione (GSH) level. Mechanistically, FBLN1 interacted with EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) and increased the protein stability of EFEMP1. More importantly, EFEMP1 silencing repressed the effect of FBLN1 on regulating EESC ferroptosis, death, and migration. Taken together, these results verify the role of the FBLN1/EFEMP1/ferroptosis pathway in the pathogenesis of EMS, and silencing of FBLN1/EFEMP1 might be an effective approach to treat EMS.", "claims": [{"id": "claim-method", "statement": "differentially expressed genes in these datasets were separately identified using GEO2R tool (log | FC | >1.5 and p < 0.05). The results from Venn diagram analysis (Venny 2.1 tool, https://bioinfogp.cnb.csic.es/tools/venny_old/index.html) showed that 9 genes (FBLN1, PDLIM3, MYH11, AEBP1, EFEMP1, CXCL12, TCEAL2, RARRES2, and PDGFRL) were concurrently upregulated and 2 genes (CXADR and MME) were concurrently downregulated in ectopic endometrial tissues compared with normal endometrial tissues (Figure 1(a)).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35127942", "locator": "sections[19] \"3.1. FBLN1 Expression Was Upregulated in Eutopic and Ectopic Endometrial Tissues with EMS\" paragraph 2", "quote": "differentially expressed genes in these datasets were separately identified using GEO2R tool (log | FC | >1.5 and p < 0.05). The results from Venn diagram analysis (Venny 2.1 tool, https://bioinfogp.cnb.csic.es/tools/venny_old/index.html) showed that 9 genes (FBLN1, PDLIM3, MYH11, AEBP1, EFEMP1, CXCL12, TCEAL2, RARRES2, and PDGFRL) were concurrently upregulated and 2 genes (CXADR and MME) were concurrently downregulated in ectopic endometrial tissues compared with normal endometrial tissues (Figure 1(a))."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are available from the corresponding author upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35127942", "locator": "sections[26] \"Data Availability\" paragraph 2", "quote": "The data used to support the findings of this study are available from the corresponding author upon request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "FBLN1/EFEMP1-dependent inhibition of ferroptosis increases endometrial stromal cell viability and migration in endometriosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35127942", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Taken together, these results verify the role of the FBLN1/EFEMP1/ferroptosis pathway in the pathogenesis of EMS, and silencing of FBLN1/EFEMP1 might be an effective approach to treat EMS."}, {"asset": "source:pmid:35127942", "locator": "sections[22] \"3.4. FBLN1 Inhibited ESC Ferroptosis, Viability, and Migration via Increasing the Stability of EFEMP1 Protein\" paragraph 2", "quote": "Taken together, the current results demonstrate that upregulated FBLN1 increased ESC viability and migration by regulating EFEMP1-dependent ferroptosis in EMS."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "FBLN1/EFEMP1-dependent inhibition of ferroptosis increases endometrial stromal cell viability and migration in endometriosis.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35127942"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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We found that the FBLN1 expression"], "order_basis": "paper_text_order:929", "id": "assay:1"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["differentially expressed genes in these datasets were separately identified using GEO2R tool (log | FC | >1.5 and p < 0.05). The results from Venn diagram analysis (Venny 2.1 tool, https://bioinfogp.cnb.csic.es/tools/venny_old/index.html) showed that 9 genes (FBLN1, PDLIM3, MYH11, AEBP1, EFEMP1, CXCL12, TCEAL2, RARRES2, and PDGFRL) were concurrently upregulated and 2 genes (CXADR and MME) were concurrently downregulated in ectopic endometrial tissues compared with normal endometrial tissues (Figure 1(a))."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}