ArticleThe Journal of clinical investigation2023
A parathyroid hormone/salt-inducible kinase signaling axis controls renal vitamin D activation and organismal calcium homeostasis.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 31 citations in OpenAlex.
- Spatial control of parathyroid hormone receptor-1 signaling dictates ligand-specific biological outcomes.Signal transduction and targeted therapy · 2026Article
- Calcium Homeostasis and Parturient Paresis in Ruminants: Mechanistic Insights and Clinical Management.Animals : an open access journal from MDPI · 2026Review
- ETV1 Couples Reciprocal FGF23 and PTH Signaling to RenalResearch square · 2026Article
- Article
- Vitamin D as a cellular endocrine system: Tissue-specific microcircuits, immune reprogramming, and metabolic resistance.iScience · 2026Review
- Inhibition of salt-inducible kinases reprograms T cells and antitumor immunity in ovarian cancer.Nature immunology · 2026Article
- Intermittent parathyroid hormone employs autonomous and non-autonomous mechanisms to drive osteogenesis from Ebf3-expressing skeletal progenitor cells.bioRxiv : the preprint server for biology · 2026Article
- Comparison of vitamin D, parathyroid hormone, and body composition in obese premenopausal and postmenopausal women.Endocrine · 2026Article
- Integrated omics reveal the effects of vitamin D deficiency on gut microbiota and plasma metabolism in experimental autoimmune uveitis.Journal of neuroinflammation · 2026Article
- Kidney organoids demonstrate that PTH1R drives a cystogenic cAMP-pPKA-pCREB axis in developmental polycystic kidney disease.American journal of physiology. Renal physiology · 2025Article
- Osteoclast-independent osteocyte dendrite defects in mice bearing the osteogenesis imperfecta-causing Sp7 R342C mutation.Bone research · 2025Article
- Phosphate in Physiological and Pathological Mineralization: Important yet Often Unheeded.MedComm · 2025Review
- The Multi-Dimensional Role of Vitamin D in the Pathophysiology and Treatment of Diabetic Foot Ulcers: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2025Review
- A mouse model of Jansen's metaphyseal chondrodysplasia for investigating disease mechanisms and candidate therapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Role of the Salt-inducible Kinases in the Endocrine Glands.Endocrinology · 2025Review
- Control of alveolar bone development, homeostasis, and socket healing by salt-inducible kinases.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Connecting Bone Remodeling and Regeneration: Unraveling Hormones and Signaling Pathways.Biology · 2025Review
- Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants.Science (New York, N.Y.) · 2025Article
- Biology of the proximal tubule in body homeostasis and kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Immune mechanisms in chronic kidney disease-mineral and bone disorder: current insights and therapeutic implications.Frontiers in medicine · 2025Review
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27 authors at 6 institutions in 2 countries.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.