PubMed:28798354 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/28798354","sourcedb":"PubMed","sourceid":"28798354","text":"Enpp1 is an anti-aging factor that regulates Klotho under phosphate overload conditions.\nControl of phosphate metabolism is crucial to regulate aging in mammals. Klotho is a well-known anti-aging factor that regulates phosphate metabolism: mice mutant or deficient in Klotho exhibit phenotypes resembling human aging. Here we show that ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) is required for Klotho expression under phosphate overload conditions. Loss-of-function Enpp1 (ttw/ttw) mice under phosphate overload conditions exhibited phenotypes resembling human aging and Klotho mutants, such as short life span, arteriosclerosis and osteoporosis, with elevated serum 1,25(OH)2D3 levels. Enpp1 (ttw/ttw) mice also exhibited significantly reduced renal Klotho expression under phosphate overload conditions, and aging phenotypes in these mice were rescued by Klotho overexpression, a low vitamin D diet or vitamin D receptor knockout. These findings indicate that Enpp1 plays a crucial role in regulating aging via Klotho expression under phosphate overload conditions.","tracks":[{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":240,"end":244},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":305,"end":310},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":499,"end":503},"obj":"OrganismTaxon"},{"id":"T4","span":{"begin":572,"end":577},"obj":"OrganismTaxon"},{"id":"T5","span":{"begin":720,"end":724},"obj":"OrganismTaxon"},{"id":"T6","span":{"begin":853,"end":857},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"10088"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"},{"id":"A3","pred":"db_id","subj":"T3","obj":"10088"},{"id":"A4","pred":"db_id","subj":"T4","obj":"9606"},{"id":"A5","pred":"db_id","subj":"T5","obj":"10088"},{"id":"A6","pred":"db_id","subj":"T6","obj":"10088"},{"subj":"T1","pred":"source","obj":"NCBITAXON"},{"subj":"T2","pred":"source","obj":"NCBITAXON"},{"subj":"T3","pred":"source","obj":"NCBITAXON"},{"subj":"T4","pred":"source","obj":"NCBITAXON"},{"subj":"T5","pred":"source","obj":"NCBITAXON"},{"subj":"T6","pred":"source","obj":"NCBITAXON"}]},{"project":"kaiyin_test","denotations":[{"id":"T4","span":{"begin":466,"end":482},"obj":"Var"},{"id":"T3","span":{"begin":483,"end":488},"obj":"Gene"},{"id":"T5","span":{"begin":540,"end":549},"obj":"Reg"},{"id":"T6","span":{"begin":629,"end":645},"obj":"Disease"},{"id":"T7","span":{"begin":650,"end":662},"obj":"Disease"},{"id":"T2","span":{"begin":669,"end":677},"obj":"PosReg"},{"id":"T1","span":{"begin":678,"end":702},"obj":"MPA"}],"relations":[{"id":"R1","pred":"CauseOf","subj":"T4","obj":"T5"},{"id":"R2","pred":"ThemeOf","subj":"T6","obj":"T5"},{"id":"R3","pred":"ThemeOf","subj":"T7","obj":"T5"},{"id":"R4","pred":"ThemeOf","subj":"T3","obj":"T4"},{"id":"R5","pred":"ThemeOf","subj":"T1","obj":"T2"},{"id":"R6","pred":"CauseOf","subj":"T4","obj":"T2"}],"attributes":[{"subj":"T4","pred":"source","obj":"kaiyin_test"},{"subj":"T3","pred":"source","obj":"kaiyin_test"},{"subj":"T5","pred":"source","obj":"kaiyin_test"},{"subj":"T6","pred":"source","obj":"kaiyin_test"},{"subj":"T7","pred":"source","obj":"kaiyin_test"},{"subj":"T2","pred":"source","obj":"kaiyin_test"},{"subj":"T1","pred":"source","obj":"kaiyin_test"}]},{"project":"name_no","denotations":[{"id":"T4","span":{"begin":466,"end":482},"obj":"Var"},{"id":"T3","span":{"begin":483,"end":488},"obj":"Gene"},{"id":"T5","span":{"begin":540,"end":549},"obj":"Reg"},{"id":"T6","span":{"begin":629,"end":645},"obj":"Disease"},{"id":"T7","span":{"begin":650,"end":662},"obj":"Disease"},{"id":"T2","span":{"begin":669,"end":677},"obj":"PosReg"},{"id":"T1","span":{"begin":678,"end":702},"obj":"MPA"}],"relations":[{"id":"R1","pred":"CauseOf","subj":"T4","obj":"T5"},{"id":"R2","pred":"ThemeOf","subj":"T6","obj":"T5"},{"id":"R3","pred":"ThemeOf","subj":"T7","obj":"T5"},{"id":"R4","pred":"ThemeOf","subj":"T3","obj":"T4"},{"id":"R5","pred":"ThemeOf","subj":"T1","obj":"T2"},{"id":"R6","pred":"CauseOf","subj":"T4","obj":"T2"}],"attributes":[{"subj":"T4","pred":"source","obj":"name_no"},{"subj":"T3","pred":"source","obj":"name_no"},{"subj":"T5","pred":"source","obj":"name_no"},{"subj":"T6","pred":"source","obj":"name_no"},{"subj":"T7","pred":"source","obj":"name_no"},{"subj":"T2","pred":"source","obj":"name_no"},{"subj":"T1","pred":"source","obj":"name_no"}]},{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":629,"end":645},"obj":"Disease"},{"id":"T2","span":{"begin":650,"end":662},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0002277"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0005298"},{"subj":"T1","pred":"source","obj":"mondo_disease"},{"subj":"T2","pred":"source","obj":"mondo_disease"}]},{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":629,"end":645},"obj":"Phenotype"},{"id":"T2","span":{"begin":650,"end":662},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0002634"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0000939"},{"subj":"T1","pred":"source","obj":"HP-phenotype"},{"subj":"T2","pred":"source","obj":"HP-phenotype"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"NCBITAXON","color":"#93ecb4","default":true},{"id":"kaiyin_test","color":"#ec9a93"},{"id":"name_no","color":"#93a5ec"},{"id":"mondo_disease","color":"#bfec93"},{"id":"HP-phenotype","color":"#ec93d9"}]}]}}