J. Wesley Pike
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Vitamin D Significantly Inhibits Carcinogenesis in the Mogp-TAg Mouse Model of Fallopian Tube Ovarian Cancer Open
Epidemiological and observational studies suggest that vitamin D has potential for the chemoprevention of ovarian cancer. The anticancer effect of vitamin D in the fallopian tube epithelium (FTE), which is now thought to harbor the precurs…
View article: In Vivo Contribution of <i>Cyp24a1</i> Promoter Vitamin D Response Elements
In Vivo Contribution of <i>Cyp24a1</i> Promoter Vitamin D Response Elements Open
CYP24A1 is a multifunctional, P450 mitochondrial enzyme that catabolizes the vitamin D hormone (calcitriol, 1,25(OH)2D3), its precursor (calcifediol, 25(OH)D3), and numerous vitamin D metabolites. In the kidney, Cyp24a1 is induced by 1,25(…
Spatial detection and consequences of nonrenal calcitriol production as assessed by targeted mass spectrometry imaging Open
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 main…
Neuropilin 2 in osteoblasts regulates trabecular bone mass in male mice Open
Introduction Neuropilin 2 (NRP2) mediates the effects of class 3 semaphorins and vascular endothelial growth factor and is implicated in axonal guidance and angiogenesis. Moreover, NRP2 expression is suggested to be involved in the regulat…
Molecular insights into mineralotropic hormone inter-regulation Open
The regulation of mineral homeostasis involves the three mineralotropic hormones PTH, FGF23 and 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ). Early research efforts focused on PTH and 1,25(OH) 2 D 3 and more recently on FGF23 have revealed …
A parathyroid hormone/salt-inducible kinase signaling axis controls renal vitamin D activation and organismal calcium homeostasis Open
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) or…
Genomic mechanisms controlling renal vitamin D metabolism Open
Vitamin D metabolism centers on regulation in the kidney of CYP27B1 induction by PTH, suppression by FGF23 and 1,25(OH)2D3, and reciprocal CYP24A1 suppression by PTH, and induction by FGF23 and 1,25(OH)2D3. This coordinated genomic regulat…
New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues Open
Recent studies of transcription have revealed an advanced set of overarching principles that govern vitamin D action on a genome-wide scale. These tenets of vitamin D transcription have emerged as a result of the application of now well-es…
Deletion of a putative promoter-proximal Tnfsf11 regulatory region in mice does not alter bone mass or Tnfsf11 expression in vivo Open
The cytokine RANKL is essential for osteoclast formation during physiological and pathological bone resorption. RANKL also contributes to lymphocyte production, development of lymph nodes and mammary glands, as well as other biological act…
Genomic Mechanisms Governing Mineral Homeostasis and the Regulation and Maintenance of Vitamin D Metabolism Open
Our recent genomic studies identified a complex kidney‐specific enhancer module located within the introns of adjacent Mettl1 (M1) and Mettl21b (M21) genes that mediate basal and PTH induction of Cyp27b1 , as well as suppression by FGF23 a…
View article: Deletion of Mediator 1 suppresses TGFβ signaling leading to changes in epidermal lineages and regeneration
Deletion of Mediator 1 suppresses TGFβ signaling leading to changes in epidermal lineages and regeneration Open
Epidermal lineages and injury induced regeneration are controlled by transcriptional programs coordinating cellular signaling and epigenetic regulators, but the mechanism remains unclear. Previous studies showed that conditional deletion o…
The unsettled science of nonrenal calcitriol production and its clinical relevance Open
The primary function of vitamin D in higher vertebrates is to regulate mineral homeostasis through direct actions on intestinal calcium and phosphate absorption, bone mineral resorption, and renal mineral reabsorption Vitamin D itself is i…
A Control Region Near the Fibroblast Growth Factor 23 Gene Mediates Response to Phosphate, 1,25(OH)2D3, and LPS In Vivo Open
Fibroblast growth factor 23 (FGF23) is a bone-derived hormone involved in the control of phosphate (P) homeostasis and vitamin D metabolism. Despite advances, however, molecular details of this gene’s regulation remain uncertain. In this r…
OR26-4 Genome-Wide Binding Profile of Phosphorylated Estrogen Receptor Reveals Association with Direct DNA Binding Open
Post-translational modifications are key regulators of protein function, providing signals that alter protein interactions and activity. Phosphorylation of estrogen receptor-α (ER) at serine 118 (pS118-ER) occurs in response to multiple st…
The Phosphorylated Estrogen Receptor <i>α</i> (ER) Cistrome Identifies a Subset of Active Enhancers Enriched for Direct ER-DNA Binding and the Transcription Factor GRHL2 Open
Posttranslational modifications are key regulators of protein function, providing cues that can alter protein interactions and cellular location. Phosphorylation of estrogen receptor α (ER) at serine 118 (pS118-ER) occurs in response to mu…
A Novel Distal Enhancer Mediates Inflammation‐, PTH‐, and Early Onset Murine Kidney Disease‐Induced Expression of the Mouse <i>Fgf23</i> Gene Open
Fibroblast growth factor 23 (FGF23) production is regulated by both calciotropic hormones and inflammation. Consistent with this, elevated FGF23 levels are associated with inflammatory markers as well as parathyroid hormone (PTH) in variou…
A kidney-specific genetic control module in mice governs endocrine regulation of the cytochrome P450 gene Cyp27b1 essential for vitamin D3 activation Open
The vitamin D endocrine system regulates mineral homeostasis through its activities in the intestine, kidney, and bone. Terminal activation of vitamin D3 to its hormonal form, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), occurs in the kidney v…
Deletion of a Distal <i>RANKL</i> Gene Enhancer Delays Progression of Atherosclerotic Plaque Calcification in Hypercholesterolemic Mice Open
Receptor activator of NF‐κB ligand (RANKL) is a TNF‐like cytokine which mediates diverse physiological functions including bone remodeling and immune regulation. RANKL has been identified in atherosclerotic lesions; however, its role in at…
The vitamin D receptor: contemporary genomic approaches reveal new basic and translational insights Open
The vitamin D receptor (VDR) is the single known regulatory mediator of hormonal 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in higher vertebrates. It acts in the nucleus of vitamin D target cells to regulate the expression of genes whose produ…
Progesterone potentiates the growth inhibitory effects of calcitriol in endometrial cancer via suppression of CYP24A1 Open
Here, we evaluated the expression of CYP24A1, a protein that inactivates vitamin D in tissues. CYP24A1 expression was increased in advanced-stage endometrial tumors compared to normal tissues. Similarly, endometrial cancer cells expressed …