{"id":"eb391c01-3fe2-5fc8-a087-63b6124440c8","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-pxr-abcb1","predicate":"mediates_dim_induction_of","statement":"DIM increased MDR1/ABCB1 expression in a PXR-dependent manner.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"0da75d16-8444-5631-9d97-2cc42fb69b0e","mechanism_event_label":"The same exposure can change a transporter as well as an enzyme.","subject":{"id":"f9deea3c-fcb8-51c8-9194-438c2ad6298b","slug":"nr1i2","display_name":"Human pregnane X receptor / SXR / PXR / NR1I2","entity_type_key":"protein"},"object":{"id":"c6139b52-4140-5622-9e33-1f6c6385265d","slug":"abcb1","display_name":"Human P-glycoprotein / ABCB1 / MDR1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"0da75d16-8444-5631-9d97-2cc42fb69b0e","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-pxr-abcb1-event","event_type":"biochemical_relationship","label":"The same exposure can change a transporter as well as an enzyme.","description":"DIM increased MDR1/ABCB1 expression in a PXR-dependent manner.","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":"inducing_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":"c6139b52-4140-5622-9e33-1f6c6385265d","slug":"abcb1","display_name":"Human P-glycoprotein / ABCB1 / MDR1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"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 same exposure can change a transporter as well as an enzyme.","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}],"evidence":[{"id":"74cceb53-8ba5-51e4-90ca-212422c7d7d4","evidence_kind":"source_excerpt","locator":"Lines 519-530","start_line":519,"end_line":530,"excerpt":"### dim-pxr-abcb1\nDIM increased MDR1/ABCB1 expression in a PXR-dependent manner.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The same exposure can change a transporter as well as an enzyme.\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}