Tissue-Wide Expression of Genes Related to Vitamin D Metabolism and FGF23 Signaling following Variable Phosphorus Intake in Pigs
2022
Maruf Hasan | Michael Oster | Henry Reyer | Siriluck Ponsuksili | Eduard Murani | Petra Wolf | Dagmar-Christiane Fischer | Klaus Wimmers
Calcium (Ca) and phosphorus (P) homeostasis is maintained by several regulators, including vitamin D and fibroblast growth factor 23 (FGF23), and their tissue-specific activation and signaling cascades. In this study, the tissue-wide expression of key genes linked to vitamin D metabolism (<i>CYP2R1</i>, <i>CYP27A1</i>, <i>CYP27B1</i>, <i>CYP24A1</i>, <i>GC</i>, <i>VDR</i>) and FGF23 signaling (<i>FGF23</i>, <i>FGFR1-4</i>, <i>KL</i>) were investigated in pigs fed conventional (trial 1) and divergent P diets (trial 2). The tissue set comprised kidney, liver, bone, lung, aorta, and gastrointestinal tract sections. Expression patterns revealed that non-renal tissues and cells (NRTC) express genes to form active vitamin D [1,25(OH)<sub>2</sub>D<sub>3</sub>] according to site-specific requirements. A low P diet resulted in higher serum calcitriol and increased <i>CYP24A1</i> expression in the small intestine, indicating local suppression of vitamin D signaling. A high P diet prompted increased mRNA abundances of <i>CYP27B1</i> for local vitamin D synthesis, specifically in bone. For FGF23 signaling, analyses revealed ubiquitous expression of <i>FGFR1-4</i>, whereas <i>KL</i> was expressed in a tissue-specific manner. Dietary P supply did not affect skeletal <i>FGF23</i>; however, <i>FGFR4</i> and <i>KL</i> showed increased expression in bone at high P supply, suggesting regulation to balance mineralization. Specific NRTC responses influence vitamin D metabolism and P homeostasis, which should be considered for a thrifty but healthy P supply.
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