| http://purl.uniprot.org/citations/36862513 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36862513 | http://www.w3.org/2000/01/rdf-schema#comment | "The renal actions of parathyroid hormone (PTH) promote 1,25-vitamin D generation; however, the signaling mechanisms that control PTH-dependent vitamin D activation remain unknown. Here, we demonstrated that salt-inducible kinases (SIKs) orchestrated renal 1,25-vitamin D production downstream of PTH signaling. PTH inhibited SIK cellular activity by cAMP-dependent PKA phosphorylation. Whole-tissue and single-cell transcriptomics demonstrated that both PTH and pharmacologic SIK inhibitors regulated a vitamin D gene module in the proximal tubule. SIK inhibitors increased 1,25-vitamin D production and renal Cyp27b1 mRNA expression in mice and in human embryonic stem cell-derived kidney organoids. Global- and kidney-specific Sik2/Sik3 mutant mice showed Cyp27b1 upregulation, elevated serum 1,25-vitamin D, and PTH-independent hypercalcemia. The SIK substrate CRTC2 showed PTH and SIK inhibitor-inducible binding to key Cyp27b1 regulatory enhancers in the kidney, which were also required for SIK inhibitors to increase Cyp27b1 in vivo. Finally, in a podocyte injury model of chronic kidney disease-mineral bone disorder (CKD-MBD), SIK inhibitor treatment stimulated renal Cyp27b1 expression and 1,25-vitamin D production. Together, these results demonstrated a PTH/SIK/CRTC signaling axis in the kidney that controls Cyp27b1 expression and 1,25-vitamin D synthesis. These findings indicate that SIK inhibitors might be helpful for stimulation of 1,25-vitamin D production in CKD-MBD."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci163627"xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Sato T."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Zhang C."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Yoon S.H."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Gupta N."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Xavier R.J."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Lee S.M."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Wang J.S."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Berdeaux R."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Fisher D.E."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Arevalo C."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Sadreyev R.I."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Pike J.W."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Anselmo A."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Adelmann C.H."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Mannstadt M."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Greka A."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Brooks D.J."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Wein M.N."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Foretz M."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Benkusky N.A."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Meyer M.B."xsd:string |
| http://purl.uniprot.org/citations/36862513 | http://purl.uniprot.org/core/author | "Strauss K."xsd:string |