| First Author | Thomas L | Year | 2024 |
| Journal | Sci Rep | Volume | 14 |
| Issue | 1 | Pages | 16997 |
| PubMed ID | 39043847 | Mgi Jnum | J:352143 |
| Mgi Id | MGI:7704728 | Doi | 10.1038/s41598-024-67839-4 |
| Citation | Thomas L, et al. (2024) Vitamin D(3) suppresses Npt2c abundance and differentially modulates phosphate and calcium homeostasis in Npt2a knockout mice. Sci Rep 14(1):16997 |
| abstractText | Vitamin D(3) is clinically used for the treatment of vitamin D(3) deficiency or osteoporosis, partially because of its role in regulating phosphate (P(i)) and calcium (Ca(2+)) homeostasis. The renal sodium-phosphate cotransporter 2a (Npt2a) plays an important role in P(i) homeostasis; however, the role of vitamin D(3) in hypophosphatemia has never been investigated. We administered vehicle or vitamin D(3) to wild-type (WT) mice or hypophosphatemic Npt2a(-/-) mice. In contrast to WT mice, vitamin D(3) treatment increased plasma P(i) levels in Npt2a(-/-) mice, despite similar levels of reduced parathyroid hormone and increased fibroblast growth factor 23. Plasma Ca(2+) was increased ~ twofold in both genotypes. Whereas WT mice were able to increase urinary P(i) and Ca(2+)/creatinine ratios, in Npt2a(-/-) mice, P(i)/creatinine was unchanged and Ca(2+)/creatinine drastically decreased, coinciding with the highest kidney Ca(2+) content, highest plasma creatinine, and greatest amount of nephrocalcinosis. In Npt2a(-/-) mice, vitamin D(3) treatment completely diminished Npt2c abundance, so that mice resembled Npt2a/c double knockout mice. Abundance of intestinal Npt2b and claudin-3 (tight junctions protein) were reduced in Npt2a(-/-) only, the latter might facilitate the increase in plasma P(i) in Npt2a(-/-) mice. Npt2a might function as regulator between renal Ca(2+) excretion and reabsorption in response to vitamin D(3). |
