Endometrial senescence is mediated by interleukin 17 receptor B signaling.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39010112", "kind": "science-record", "revision": 2, "content_hash": "sha256:e9ed5583f299533983431b4991927797f659380bcfc8ac863d17cd85fc75c631", "created_at": "2026-11-01T20:29:05Z", "updated_at": "2026-11-01T21:33:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Endometrial senescence is mediated by interleukin 17 receptor B signaling.", "doi": "10.1186/s12964-024-01740-5", "pmid": "39010112", "authors": ["Keiko Kawamura", "Yumiko Matsumura", "Teruhiko Kawamura", "Hiromitsu Araki", "Norio Hamada", "Kazutaka Kuramoto", "Hiroshi Yagi", "Ichiro Onoyama", "Kazuo Asanoma", "Kiyoko Kato"], "journal": "Cell communication and signaling : CCS", "year": 2024, "abstract": "BACKGROUND: We previously identified Il17RB, a member of the IL17 superfamily, as a candidate marker gene for endometrial aging. While IL17RB has been linked to inflammation and malignancies in several organ systems, its function in the endometrium has not been investigated and is thus poorly understood. In the present study, we performed a functional analysis of this receptor with the aim of determining the effects of its age-associated overexpression on the uterine environment.\nMETHODS: We analyzed IL17RB-related signaling pathways and downstream gene expression in an immortalized human endometrial glandular epithelial cell line (\"hEM\") forced to express the receptor via lentiviral transduction (\"IL17RB-hEM\"). We also prepared endometrial organoids from human endometrial tissue sourced from hysterectomy patients (\"patient-derived EOs\") and exposed them to cytokines that are upregulated by IL17RB expression to investigate changes in organoid-forming capacity and senescence markers. We analyzed RNA-seq data (GEO accession number GSE132886) from our previous study to identify the signaling pathways associated with altered IL17RB expression. We also analyzed the effects of the JNK pathway on organoid-forming capacity.\nRESULTS: Stimulation with interleukin 17B enhanced the NF-κB pathway in IL17RB-hEM, resulting in significantly elevated expression of the genes encoding the senescence associated secretory phenotype (SASP) factors IL6, IL8, and IL1β. Of these cytokines, IL1β inhibited endometrial organoid growth. Bioinformatics analysis showed that the JNK signaling pathway was associated with age-related variation in IL17RB expression. When IL17RB-positive cells were cultured in the presence of IL17B, their organoid-forming capacity was slightly but non-significantly lower than in unexposed IL17RB-positive cells, but when IL17B was paired with a JNK inhibitor (SP600125), it was restored to control levels. Further, IL1β exposure significantly reduced organoid-forming capacity and increased p21 expression in endometrial organoids relative to non-exposure (control), but when IL1β was paired with SP600125, both indicators were restored to levels comparable to the control condition.\nCONCLUSIONS: We have revealed an association between IL17RB, whose expression increases in the endometrial glandular epithelium with advancing age, and cellular senescence. Using human endometrial organoids as in vitro model, we found that IL1β inhibits cell proliferation and leads to endometrial senescence via the JNK pathway.", "claims": [{"id": "claim-method", "statement": "We used Student’s t-tests for comparisons between two independent groups and Dunnett’s multiple comparison test for multiple comparisons.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39010112", "locator": "sections[17] \"Statistical analysis\" paragraph 2", "quote": "We used Student’s t-tests for comparisons between two independent groups and Dunnett’s multiple comparison test for multiple comparisons."}], "state": "complete"}, {"id": "claim-data-access", "statement": "No datasets were generated or analysed during the current study.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39010112", "locator": "sections[32] \"Availability of data and materials\" paragraph 2", "quote": "No datasets were generated or analysed during the current study."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:39010112"], "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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This series of experiments used endome"], "order_basis": "paper_text_order:859", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["capacity and senescence markers. We analyzed RNA-seq data (GEO accession number GSE132886) from o"], "order_basis": "paper_text_order:1040", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["expression. When IL17RB-positive cells were cultured in the presence of IL17B, their organoid-formin", "s conditions at each passage. When they were cultured in ExM containing IL6, their organoid-forming c", "y in the 100 ng/ml condition (Fig. 2A). When cultured in ExM containing IL1β, their organoid-forming", "y patients. (A) Endometrial organoids (EM_2) cultured in ExM containing IL6 (10, 100 ng/ml) or IL8 (1"], "order_basis": "paper_text_order:1723", "id": "assay:3"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["d evaluated their fluorescence intensity via flow cytometry. Relative to the control condition (non-expo", "by chronic IL1β stimulation. A SPiDER-β-Gal flow cytometry of endometrial organoids (EM_2, passage 3).", "e endometrial cells and separated them using flow cytometry to identify functional differences attributa", "ditional file 3: Fig. S3. (A-B) SPiDER-β-Gal flow cytometry of endometrial organoids. Horizontal axis: S"], "order_basis": "paper_text_order:6972", "id": "assay:4"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["e control condition (non-exposure), SA-β-gal immunofluorescence did not increase in response to either IL6 o"], "order_basis": "paper_text_order:7047", "id": "assay:5"}, {"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": ["onors (Supplementary Fig. S2C–D). To exclude apoptosis as the cause of the reduced organoid-forming", "long-term exposure to IL1β, we conducted an apoptosis assay. Endometrial organoids exposed to IL1β", "ions; however, their rates of early and late apoptosis were no higher than in the control condition", "(yellow area: SA-β-gal-positive cells). (B) Apoptosis assay using endometrial organoids (EM_6, pas"], "order_basis": "paper_text_order:7943", "id": "assay:6"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["0, 100 ng/ml). Expression was quantified via RT-qPCR relative to an endogenous control (18 S rRNA", "0, 100 ng/ml). Expression was quantified via RT-qPCR relative to an endogenous control (18S rRNA)", "0, 100 ng/ml). Expression was quantified via RT-qPCR relative to an endogenous control (HPRT1). E", "100 ng/ml). Expression was quantified via RT-qPCR relative to an endogenous control (18 S rRNA"], "order_basis": "paper_text_order:8909", "id": "assay:7"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["itional file 8: Fig. S8. Original, uncropped immunoblots of Fig.1B, 1D, 5B-C and 6A-B. Red regions ar"], "order_basis": "paper_text_order:14103", "id": "assay:8"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pearson_r"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Pearson's correlation"], "order_basis": "consumes_earlier_output", "id": "assay:9"}]}