FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2980919728> ?p ?o ?g. }

• W2980919728 endingPage "105500" @default.
• W2980919728 startingPage "105500" @default.
• W2980919728 abstract "Cyp27b1 and Cyp24a1 are reciprocally regulated in the kidney by the key hormones PTH, FGF23, and 1,25(OH)2D3. Our recent genomic studies in mice identified a complex kidney-specific enhancer module located within the introns of adjacent Mettl1 (M1) and Mettl21b (M21) genes that mediate basal and PTH induction of Cyp27b1 as well as suppression by FGF23 and 1,25(OH)2D3. Gross deletion of these segments in mice has severe consequences on skeletal health, and directly affects Cyp27b1 expression in the kidney. Deletion of both M1 and M21 submodules together fully eliminates basal Cyp27b1 expression in the kidney, leading to a systemic and skeletal phenotype similar to that of the Cyp27b1-KO mouse due to depletion of 1,25(OH)2D3 and high PTH. Cyp24a1 levels in the double KO mouse were low due to compensatory regulation by elevated PTH and reduced FGF23. However, expression of Cyp27b1 and retention of its regulation by inflammation (LPS) in the NRTCs remained unperturbed. Dietary normalization of calcium, phosphate, PTH, and FGF23 rescues this aberrant phenotype and normalizes the skeletal issues. Cyp24a1 is controlled by its own unique enhancers for 1,25(OH)2D3, FGF23, and PTH. We were also able to eliminate these activities in mice. Collectively, the hormone-mediated enhancer regulation of both Cyp27b1 and Cyp24a1 in the kidney is responsible for the circulating levels of 1,25(OH)2D3 in the blood which in turn primarily affects calcium and phosphate regulation. Importantly, we can now manipulate this system with our enhancer deletion animal models to study 1,25(OH)2D3 production in non-renal target cells and tissues not only in disease, where it is known to affect the immune system, but also in healthy individuals. Here we will review our studies that have defined a finely balanced homeostatic control mechanism employed by PTH and FGF23 with catastrophic toxicity protection from 1,25(OH)2D3 in the genomic regulation of vitamin D metabolism and its accompanied control of mineral maintenance." @default.
• W2980919728 created "2019-10-25" @default.
• W2980919728 creator A5023230304 @default.
• W2980919728 creator A5049270000 @default.
• W2980919728 date "2020-02-01" @default.
• W2980919728 modified "2023-10-03" @default.
• W2980919728 title "Mechanistic homeostasis of vitamin D metabolism in the kidney through reciprocal modulation of Cyp27b1 and Cyp24a1 expression" @default.
• W2980919728 cites W1531821806 @default.
• W2980919728 cites W1945579058 @default.
• W2980919728 cites W1965937833 @default.
• W2980919728 cites W1971194043 @default.
• W2980919728 cites W1978661875 @default.
• W2980919728 cites W1986689077 @default.
• W2980919728 cites W1990796758 @default.
• W2980919728 cites W2000300100 @default.
• W2980919728 cites W2002494594 @default.
• W2980919728 cites W2005328221 @default.
• W2980919728 cites W2017290177 @default.
• W2980919728 cites W2017743594 @default.
• W2980919728 cites W2017907756 @default.
• W2980919728 cites W2030338624 @default.
• W2980919728 cites W2040959543 @default.
• W2980919728 cites W2045435533 @default.
• W2980919728 cites W2047032063 @default.
• W2980919728 cites W2054475366 @default.
• W2980919728 cites W2061650108 @default.
• W2980919728 cites W2064148273 @default.
• W2980919728 cites W2064815984 @default.
• W2980919728 cites W2067649223 @default.
• W2980919728 cites W2069981790 @default.
• W2980919728 cites W2101749257 @default.
• W2980919728 cites W2112293785 @default.
• W2980919728 cites W2114841834 @default.
• W2980919728 cites W2117757143 @default.
• W2980919728 cites W2142544310 @default.
• W2980919728 cites W2157698829 @default.
• W2980919728 cites W2160051211 @default.
• W2980919728 cites W2164044577 @default.
• W2980919728 cites W2167465564 @default.
• W2980919728 cites W2169244146 @default.
• W2980919728 cites W2170039745 @default.
• W2980919728 cites W2247766769 @default.
• W2980919728 cites W2747982551 @default.
• W2980919728 cites W2792664678 @default.
• W2980919728 cites W2878721160 @default.
• W2980919728 cites W2943450213 @default.
• W2980919728 cites W2969979551 @default.
• W2980919728 cites W4245958271 @default.
• W2980919728 doi "https://doi.org/10.1016/j.jsbmb.2019.105500" @default.
• W2980919728 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6954286" @default.
• W2980919728 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31629064" @default.
• W2980919728 hasPublicationYear "2020" @default.
• W2980919728 type Work @default.
• W2980919728 sameAs 2980919728 @default.
• W2980919728 citedByCount "36" @default.
• W2980919728 countsByYear W29809197282020 @default.
• W2980919728 countsByYear W29809197282021 @default.
• W2980919728 countsByYear W29809197282022 @default.
• W2980919728 countsByYear W29809197282023 @default.
• W2980919728 crossrefType "journal-article" @default.
• W2980919728 hasAuthorship W2980919728A5023230304 @default.
• W2980919728 hasAuthorship W2980919728A5049270000 @default.
• W2980919728 hasBestOaLocation W29809197282 @default.
• W2980919728 hasConcept C124490489 @default.
• W2980919728 hasConcept C126322002 @default.
• W2980919728 hasConcept C134018914 @default.
• W2980919728 hasConcept C138885662 @default.
• W2980919728 hasConcept C179639408 @default.
• W2980919728 hasConcept C2777742833 @default.
• W2980919728 hasConcept C2780091579 @default.
• W2980919728 hasConcept C41895202 @default.
• W2980919728 hasConcept C62231903 @default.
• W2980919728 hasConcept C63645605 @default.
• W2980919728 hasConcept C71924100 @default.
• W2980919728 hasConcept C76743606 @default.
• W2980919728 hasConcept C86803240 @default.
• W2980919728 hasConceptScore W2980919728C124490489 @default.
• W2980919728 hasConceptScore W2980919728C126322002 @default.
• W2980919728 hasConceptScore W2980919728C134018914 @default.
• W2980919728 hasConceptScore W2980919728C138885662 @default.
• W2980919728 hasConceptScore W2980919728C179639408 @default.
• W2980919728 hasConceptScore W2980919728C2777742833 @default.
• W2980919728 hasConceptScore W2980919728C2780091579 @default.
• W2980919728 hasConceptScore W2980919728C41895202 @default.
• W2980919728 hasConceptScore W2980919728C62231903 @default.
• W2980919728 hasConceptScore W2980919728C63645605 @default.
• W2980919728 hasConceptScore W2980919728C71924100 @default.
• W2980919728 hasConceptScore W2980919728C76743606 @default.
• W2980919728 hasConceptScore W2980919728C86803240 @default.
• W2980919728 hasFunder F4320310176 @default.
• W2980919728 hasLocation W29809197281 @default.
• W2980919728 hasLocation W29809197282 @default.
• W2980919728 hasOpenAccess W2980919728 @default.
• W2980919728 hasPrimaryLocation W29809197281 @default.
• W2980919728 hasRelatedWork W1824985903 @default.
• W2980919728 hasRelatedWork W2009745211 @default.
• W2980919728 hasRelatedWork W2012270105 @default.
• W2980919728 hasRelatedWork W2037727994 @default.

• next