Spatial detection and consequences of nonrenal calcitriol production as assessed by targeted mass spectrometry imaging.

Autor: Meyer MB; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA., Lee SM; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA., Cichanski SR; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA., Cobice DF; Mass Spectrometry Centre, Biomedical Sciences Research Institute (BMSRI), School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom., Pike JW; Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2024 Jun 25; Vol. 9 (15). Date of Electronic Publication: 2024 Jun 25.
DOI: 10.1172/jci.insight.181763
Abstrakt: The immune benefits of vitamin D3 supplementation beyond calcium and phosphate maintenance are highly clinically debated. Kidney expression of CYP27B1 is the source of endocrine, circulating 1,25(OH)2D3 (active form of vitamin D) that maintains serum calcium and phosphate. 1,25(OH)2D3 may also be made by the CYP27B1 enzyme in nonrenal cells, like immune cells, in a process driven by cellular availability of 25(OH)D3 and inflammation. Due to the endocrine nature of 1,25(OH)2D3 in circulation, it is difficult to discern between these 2 sources. We recently created a regulatory deletion model of Cyp27b1 (M1/M21-DIKO) where mice have normal inflammatory-regulated Cyp27b1 expression in nonrenal tissues (unlike global Cyp27b1-KO) but no expression within the kidney. Here, utilizing on-tissue chemical derivatization and matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI), we investigated the distribution of 1,25(OH)2D3 and 25(OH)D3 in the kidney, liver, spleen, and thymus. MALDI-MSI demonstrated increased 1,25(OH)2D3 in nonrenal tissues such as the spleen after vitamin D3 supplementation in M1/M21-DIKO mice. Additionally, from this, we found increased Il4 and decreased Tnfa in the spleen after vitamin D3 supplementation. Taken together, these data demonstrate nonrenal production of 1,25(OH)2D3 in vivo and provide a consequence of vitamin D3 supplementation and nonrenal 1,25(OH)2D3 production in cytokine changes.
Databáze: MEDLINE