Functional Analysis of Estrogen Receptor 1 in Diabetic Wound Healing: A Knockdown Cell-Based and Bioinformatic Study.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33338031", "kind": "science-record", "revision": 5, "content_hash": "sha256:1b7a8f29f45be46f04e38195c21ea99facbad8c08dbb240e8c052d4e5f704d19", "created_at": "2026-11-01T17:34:30Z", "updated_at": "2026-11-01T22:45:50Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Functional Analysis of Estrogen Receptor 1 in Diabetic Wound Healing: A Knockdown Cell-Based and Bioinformatic Study.", "doi": "10.12659/MSM.928788", "pmid": "33338031", "authors": ["Sha Qi", "Qiong Han", "Danmou Xing", "Long Qian", "Xiang Yu", "Dong Ren", "Huan Wang", "Quan Chen"], "journal": "Medical science monitor : international medical journal of experimental and clinical research", "year": 2020, "abstract": "BACKGROUND Diabetic wound (DW) treatment is a serious challenge for clinicians, and the underlying mechanisms of DWs remain elusive. We sought to identify the critical genes in the development of DWs and provide potential targets for DW therapies. MATERIAL AND METHODS Datasets of GSE38396 from the Gene Expression Omnibus (GEO) database were reviewed. Pathway analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology term analyses were carried out, and Cytoscape software (Cytoscape 3.7.2) was used to construct the protein interaction network. Serum samples from patients with diabetes and control participants were collected, and the expression of estrogen receptor 1 (ESR1) was measured by quantitative reverse-transcription polymerase chain reaction. In addition, the function of ESR1 in human skin fibroblasts was investigated in vitro. RESULTS Eight samples were analyzed using the Morpheus online tool, which identified 637 upregulated and 448 downregulated differentially expressed genes. The top 5 KEGG pathways of upregulated differentially expressed genes were associated with sphingolipid metabolism, estrogen signaling, ECM-receptor interaction, MAPK signaling, and PI3K-Akt signaling. The hub genes for DWs were JUN, ESR1, CD44, SMARCA4, MMP2, BMP4, GSK3B, WDR5, PTK2, and PTGS2. JUN, MMP2, and ESR1 were the upregulated hub genes, and ESR1 was found to be consistently enriched in DW patients. Inhibition of ESR1 had a stimulative role in human skin fibroblasts. CONCLUSIONS ESR1 was identified as a crucial gene in the development of DWs, which suggests potential therapeutic targets for DW healing.", "claims": [{"id": "claim-method", "statement": "Paired data were compared using t tests, and 1-way analysis of variance with Tukey’s post hoc test was used to analyze data from 3 or more groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33338031", "locator": "sections[12] \"Statistical analysis\" paragraph 2", "quote": "Paired data were compared using t tests, and 1-way analysis of variance with Tukey’s post hoc test was used to analyze data from 3 or more groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression profile GSE38396 was obtained from the GEO database. There were 8 samples in this microarray data, which included 4 normal individuals and 4 patients with type 2 diabetes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33338031", "locator": "sections[14] \"Identification of DEGs\" paragraph 2", "quote": "The gene expression profile GSE38396 was obtained from the GEO database. There were 8 samples in this microarray data, which included 4 normal individuals and 4 patients with type 2 diabetes."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ESR1 was identified as a crucial gene in the development of DWs, which suggests potential therapeutic targets for DW healing.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:33338031", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "ESR1 was identified as a crucial gene in the development of DWs, which suggests potential therapeutic targets for DW healing."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "ESR1 was identified as a crucial gene in the development of DWs, which suggests potential therapeutic targets for DW healing.", "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:33338031"], "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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Cell culture and transfection Human skin fibroblasts (HSFs; FuHeng Biology", "d, NY, USA) with 10% fetal bovine serum. For transfection, Lipofectamine 3000 (ThermoFisher Scientific", "t 37°C with 5% CO2 and 95% humidity. For the transfection of mRNA and siRNA oligos steps, constructs f"], "order_basis": "paper_text_order:27", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["(HSFs; FuHeng Biology, Shanghai, China) were cultured in high-glucose Dulbecco’s modified Eagle’s med"], "order_basis": "paper_text_order:2191", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["eration-related genes were increased and the apoptosis-related genes were decreased after ESR1 knoc", "of HSFs was then investigated in vitro. 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