ArticleAging2024
Tsc22d3 promotes morphine tolerance in mice through the GPX4 ferroptosis pathway.
Article in Aging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Single-cell RNA Sequencing Analysis Reveals the Molecular Mechanisms of Neutrophil Dysfunction in Chronic Bone Infection.Current medicinal chemistry · 2026Article
- Mechanisms and Therapeutic Potential of GPX4 in Pain Modulation.Pain and therapy · 2025Review
- Identification and Validation of a New Functional GeneStem cells international · 2025Article
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3 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundMorphine tolerance refers to gradual reduction in response to drug with continuous or repeated use of morphine, requiring higher doses to achieve same effect.
methodsThe 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.
results500 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.
conclusionsTsc22d3 is highly expressed in brain tissue of morphine-tolerant mice, activating ferroptosis pathway, enhancing apoptosis, promoting inflammatory responses in brain cells.
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