{"id":"760b4789-3f2f-548b-9c3a-68382bd1976d","stable_key":"dff9f743-3766-5f20-a71e-d6d2bd5bfb6f:va-retinoic-acid-isx-feedback","predicate":"induces","statement":"Retinoic-acid receptor signaling increased intestinal ISX expression.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"82c3eec6-13e0-5a6b-8957-2a900920f48b","mechanism_event_label":"The active retinoid metabolite induces a brake on further precursor uptake.","subject":{"id":"05487b29-8c59-5af8-83cf-cf9c79c5ecb8","slug":"all-trans-retinoic-acid","display_name":"All-trans-retinoic acid","entity_type_key":"small_molecule"},"object":{"id":"720be86d-9f3e-5f54-9160-1772c0bcccfa","slug":"isx","display_name":"Intestine-specific homeobox protein / ISX","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"82c3eec6-13e0-5a6b-8957-2a900920f48b","stable_key":"dff9f743-3766-5f20-a71e-d6d2bd5bfb6f:va-retinoic-acid-isx-feedback-event","event_type":"biochemical_relationship","label":"The active retinoid metabolite induces a brake on further precursor uptake.","description":"Retinoic-acid receptor signaling increased intestinal ISX expression.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"0453bf0c-3c7c-5275-9b9e-8d7f01613b51","slug":"rar-family","display_name":"Retinoic acid receptor family","entity_type_key":"protein_family"},"role":"signaling-mediators","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"05487b29-8c59-5af8-83cf-cf9c79c5ecb8","slug":"all-trans-retinoic-acid","display_name":"All-trans-retinoic acid","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"720be86d-9f3e-5f54-9160-1772c0bcccfa","slug":"isx","display_name":"Intestine-specific homeobox protein / ISX","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_location","value_text":"Abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse diet/retinoic-acid interventions and human cell lines.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Retinoic-acid treatment with receptor-dependent tests.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Pharmacological treatment supports feedback circuitry, not a universal dietary threshold.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin A research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-a","display_name":"Vitamin A","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Mus musculus and Homo sapiens cell lines","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"outcome","value_text":"Retinoic-acid receptor signaling increased intestinal ISX expression.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The active retinoid metabolite induces a brake on further precursor uptake.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[va-lobo-2010] ISX is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin A production (2010). https://pubmed.ncbi.nlm.nih.gov/20061533/ DOI: 10.1096/fj.09-150995","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Intestine and cultured cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"6c47d26c-21b0-5655-b25d-923607135d8b","evidence_kind":"source_excerpt","locator":"Lines 260-272","start_line":260,"end_line":272,"excerpt":"### va-retinoic-acid-isx-feedback\nRetinoic-acid receptor signaling increased intestinal ISX expression.\nCondition category: normal\nnutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The active retinoid metabolite induces a brake on further precursor uptake.\norganism: Mus musculus and Homo sapiens cell lines\ntissue_or_cell_type: Intestine and cultured cells\nexperimental_model: Mouse diet/retinoic-acid interventions and human cell lines.\nlimitations: Pharmacological treatment supports feedback circuitry, not a universal dietary threshold.\nexposure: Retinoic-acid treatment with receptor-dependent tests.\noutcome: Retinoic-acid receptor signaling increased intestinal ISX expression.\nevidence_location: Abstract\n[va-lobo-2010] ISX is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin A production (2010). https://pubmed.ncbi.nlm.nih.gov/20061533/ DOI: 10.1096/fj.09-150995","model_system":"Mouse diet/retinoic-acid interventions and human cell lines.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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