{"id":"b5167d5f-5715-56c3-a2ae-500e512db418","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-hif2-loss","predicate":"loss_reduces","statement":"Intestinal Hif2a deletion lowered serum and liver iron and markedly reduced liver hepcidin expression.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e8faa6cd-a9a7-5e22-ad2c-ff85b3645240","mechanism_event_label":"A hormonal attempt to increase iron availability did not replace the missing intestinal regulator.","subject":{"id":"03430527-8d72-5895-98e1-f66f221f0887","slug":"mouse-epas1","display_name":"Mouse hypoxia-inducible factor 2 alpha / Epas1","entity_type_key":"protein"},"object":{"id":"62f35ef9-e8bf-5b02-85f8-bc2f281f30dd","slug":"serum-iron-concentration","display_name":"Serum iron concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e8faa6cd-a9a7-5e22-ad2c-ff85b3645240","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-hif2-loss-event","event_type":"biochemical_relationship","label":"A hormonal attempt to increase iron availability did not replace the missing intestinal regulator.","description":"Intestinal Hif2a deletion lowered serum and liver iron and markedly reduced liver hepcidin expression.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2a597498-5364-5b2c-95e2-39010dc0084c","slug":"mouse-hamp","display_name":"Mouse hepcidin / Hamp","entity_type_key":"protein"},"role":"compensatory_response","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"03430527-8d72-5895-98e1-f66f221f0887","slug":"mouse-epas1","display_name":"Mouse hypoxia-inducible factor 2 alpha / Epas1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"62f35ef9-e8bf-5b02-85f8-bc2f281f30dd","slug":"serum-iron-concentration","display_name":"Serum iron concentration","entity_type_key":"cellular_process"},"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/iron-research/19352007.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"623fedcdd407c02879254b087510cff95b61336f7605c2430f51ab75ac550040\", \"start_char\": 0, \"end_char\": 1411, \"text_sha256\": \"623fedcdd407c02879254b087510cff95b61336f7605c2430f51ab75ac550040\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Conditional intestinal Hif1a/Hif2a knockout","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Separate Hif1a versus Hif2a deletion","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"HIF isoforms were not interchangeable in this mouse experiment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iron research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mice","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A hormonal attempt to increase iron availability did not replace the missing intestinal regulator.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iron-p19352007] HIF-2alpha, but not HIF-1alpha, promotes iron absorption in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19352007/ DOI: 10.1172/jci38499","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Duodenal epithelium and systemic iron","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":"67e88018-6738-560f-b9f5-cda4dedbc09f","evidence_kind":"source_excerpt","locator":"Lines 862-873","start_line":862,"end_line":873,"excerpt":"### iron-hif2-loss\nIntestinal Hif2a deletion lowered serum and liver iron and markedly reduced liver hepcidin expression.\nCondition category: machinery_impairment\nnutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A hormonal attempt to increase iron availability did not replace the missing intestinal regulator.\norganism: Mice\ntissue_or_cell_type: Duodenal epithelium and systemic iron\nexperimental_model: Conditional intestinal Hif1a/Hif2a knockout\nlimitations: HIF isoforms were not interchangeable in this mouse experiment.\nexposure: Separate Hif1a versus Hif2a deletion\nevidence_span: {\"source_cache\": \"artifacts/iron-research/19352007.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"623fedcdd407c02879254b087510cff95b61336f7605c2430f51ab75ac550040\", \"start_char\": 0, \"end_char\": 1411, \"text_sha256\": \"623fedcdd407c02879254b087510cff95b61336f7605c2430f51ab75ac550040\"}\n[iron-p19352007] HIF-2alpha, but not HIF-1alpha, promotes iron absorption in mice. 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