{"id":"c38b3205-30e3-5862-9f74-4395d2023646","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-pxr-loss-cyp3a4","predicate":"knockdown_attenuates_dim_induction_of","statement":"PXR knockdown or inhibition attenuated DIM-induced CYP3A4 expression.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"b73b7c47-4cf9-5bae-85e8-0046a6d49892","mechanism_event_label":"The response weakened when a required signaling component was blocked.","subject":{"id":"f9deea3c-fcb8-51c8-9194-438c2ad6298b","slug":"nr1i2","display_name":"Human pregnane X receptor / SXR / PXR / NR1I2","entity_type_key":"protein"},"object":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"b73b7c47-4cf9-5bae-85e8-0046a6d49892","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-pxr-loss-cyp3a4-event","event_type":"biochemical_relationship","label":"The response weakened when a required signaling component was blocked.","description":"PXR knockdown or inhibition attenuated DIM-induced CYP3A4 expression.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"role":"exposure","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f9deea3c-fcb8-51c8-9194-438c2ad6298b","slug":"nr1i2","display_name":"Human pregnane X receptor / SXR / PXR / NR1I2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dim-research/25542144.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d\", \"start_char\": 0, \"end_char\": 1440, \"text_sha256\": \"426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Promoter reporters, expression, knockdown and transport assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"DIM exposure with PXR inhibition or knockdown controls","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human hepatocytes and intestinal cell models","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The response weakened when a required signaling component was blocked.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"PXR-regulated CYP3A4 and ABCB1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"daa7e2c8-77a9-50d1-8195-638bf734de06","evidence_kind":"source_excerpt","locator":"Lines 545-556","start_line":545,"end_line":556,"excerpt":"### dim-pxr-loss-cyp3a4\nPXR knockdown or inhibition attenuated DIM-induced CYP3A4 expression.\nCondition category: machinery_impairment\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The response weakened when a required signaling component was blocked.\norganism: Human hepatocytes and intestinal cell models\ntissue_or_cell_type: PXR-regulated CYP3A4 and ABCB1\nexperimental_model: Promoter reporters, expression, knockdown and transport assays\nlimitations: Cell-model induction, not a quantified human interaction. Older liver-slice assays showed little CYP3A4 response under their conditions.\nexposure: DIM exposure with PXR inhibition or knockdown controls\nevidence_span: {\"source_cache\": \"artifacts/dim-research/25542144.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d\", \"start_char\": 0, \"end_char\": 1440, \"text_sha256\": \"426f3b5a572a469ad9a9d03c6fd7919eacd55c3995b510fdefffac551a09b16d\"}\n[dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015","model_system":"Promoter reporters, expression, knockdown and transport assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [dim-p25542144] Diindolylmethane, a naturally occurring compound, induces CYP3A4 and MDR1 gene expression by activating human PXR. (2015). https://pubmed.ncbi.nlm.nih.gov/25542144/ DOI: 10.1016/j.toxlet.2014.12.015","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"b6d70682-97f9-5893-a03c-f9f88836033c","stable_key":"import-182336c6-ed36-5ec6-8a09-25c31096262e","title":"Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"31e14060de904976d2f5d439f2bc9c8a99a72d34626c562c78429025e050d404","revision_id":"611094c1-a9cf-5b9b-b255-ac70b571696a","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}