Tsc22d3 promotes morphine tolerance in mice through the GPX4 ferroptosis pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38843390", "kind": "science-record", "revision": 4, "content_hash": "sha256:cdc201d4ee1a477553c6cde55d9aade499afdaf2c5e62d8dd473ba7811ae6ba2", "created_at": "2026-11-01T19:20:47Z", "updated_at": "2026-11-01T22:54:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Tsc22d3 promotes morphine tolerance in mice through the GPX4 ferroptosis pathway.", "doi": "10.18632/aging.205903", "pmid": "38843390", "authors": ["Yan Chen", "Shan Li", "Fenghui Guo"], "journal": "Aging", "year": 2024, "abstract": "BACKGROUND: Morphine tolerance refers to gradual reduction in response to drug with continuous or repeated use of morphine, requiring higher doses to achieve same effect.\nMETHODS: The morphine tolerance dataset GSE7762 profiles, obtained from gene expression omnibus (GEO) database, were used to identify differentially expressed genes (DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) was applied to explore core modules of DEGs related to morphine tolerance. Core genes were input into Comparative Toxicogenomics Database (CTD). Animal experiments were performed to validate role of Tsc22d3 in morphine tolerance and its relationship with ferroptosis-related pathway.\nRESULTS: 500 DEGs were identified. DEGs were primarily enriched in negative regulation of brain development, neuronal apoptosis processes, and neurosystem development. Core gene was identified as Tsc22d3. Tsc22d3 gene-associated miRNAs were mmu-miR-196b-5p and mmu-miR-196a-5p. Compared to Non-morphine tolerant group, Tsc22d3 expression was significantly upregulated in Morphine tolerant group. Tsc22d3 expression was upregulated in Morphine tolerant+Tsc22d3_OE, expression of HIF-1alpha, GSH, GPX4 in GPX4 ferroptosis-related pathway showed a more pronounced decrease. As Tsc22d3 expression was downregulated in Morphine tolerant+Tsc22d3_KO, expression of HIF-1alpha, GSH, GPX4 in GPX4 ferroptosis-related pathway exhibited a more pronounced increase. Upregulation of Tsc22d3 in Morphine tolerant+Tsc22d3_OE led to a more pronounced increase in expression of apoptosis proteins (P53, Caspase-3, Bax, SMAC, FAS). The expression of inflammatory factors (IL6, TNF-alpha, CXCL1, CXCL2) showed a more pronounced increase with upregulated Tsc22d3 expression in Morphine tolerant+Tsc22d3_OE.\nCONCLUSIONS: Tsc22d3 is highly expressed in brain tissue of morphine-tolerant mice, activating ferroptosis pathway, enhancing apoptosis, promoting inflammatory responses in brain cells.", "claims": [{"id": "claim-method", "statement": "The R package “limma” was used for probe summarization and background correction of the gene expression matrix from GSE7762. The Benjamini-Hochberg method was employed to adjust the raw p-values. The fold change (FC) was calculated using the false discovery rate (FDR). The cutoff criterion for DEGs was set at P < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38843390", "locator": "sections[20] \"DEGs selection\" paragraph 2", "quote": "The R package “limma” was used for probe summarization and background correction of the gene expression matrix from GSE7762. The Benjamini-Hochberg method was employed to adjust the raw p-values. The fold change (FC) was calculated using the false discovery rate (FDR). The cutoff criterion for DEGs was set at P < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38843390", "locator": "sections[29] \"Data availability\" paragraph 2", "quote": "The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Tsc22d3 is highly expressed in brain tissue of morphine-tolerant mice, activating ferroptosis pathway, enhancing apoptosis, promoting inflammatory responses in brain cells.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38843390", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Tsc22d3 is highly expressed in brain tissue of morphine-tolerant mice, activating ferroptosis pathway, enhancing apoptosis, promoting inflammatory responses in brain cells."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Tsc22d3 is highly expressed in brain tissue of morphine-tolerant mice, activating ferroptosis pathway, enhancing apoptosis, promoting inflammatory responses in brain cells.", "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:38843390"], "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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