Lithocholic acid increases intestinal phosphate and calcium absorption in a vitamin D receptor dependent but transcellular pathway independent manner

2020 ◽  
Vol 97 (6) ◽  
pp. 1164-1180 ◽  
Author(s):  
Nobuhiro Hashimoto ◽  
Isao Matsui ◽  
Satoshi Ishizuka ◽  
Kazunori Inoue ◽  
Ayumi Matsumoto ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Calcium Absorption ◽  
Lithocholic Acid ◽  
Independent Manner ◽  
Transcellular Pathway

Lithocholic Acid-Based Design of Noncalcemic Vitamin D Receptor Agonists

2021 ◽  
pp. 104878
Author(s):  
Sunil Gaikwad ◽  
Carmen M. González ◽  
Daniel Vilariño ◽  
Gonzalo Lasanta ◽  
Carmen Villaverde ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Lithocholic Acid ◽  
Receptor Agonists

Structural Insights into the Molecular Mechanism of Vitamin D Receptor Activation by Lithocholic Acid Involving a New Mode of Ligand Recognition

2014 ◽  
Vol 57 (11) ◽  
pp. 4710-4719 ◽  
Author(s):  
Anna Y. Belorusova ◽  
Jérôme Eberhardt ◽  
Noëlle Potier ◽  
Roland H. Stote ◽  
Annick Dejaegere ◽  
...  
Keyword(s):  
Vitamin D ◽  
Molecular Mechanism ◽  
Vitamin D Receptor ◽  
Lithocholic Acid ◽  
Receptor Activation ◽  
Ligand Recognition ◽  
Structural Insights

scholarly journals 25-Hydroxyvitamin D Inhibits Hepatitis C Virus Production in Hepatocellular Carcinoma Cell Line by a Vitamin D Receptor-Independent Mechanism

2019 ◽  
Vol 20 (9) ◽  
pp. 2367 ◽  
Author(s):  
Amiram Ravid ◽  
Noa Rapaport ◽  
Assaf Issachar ◽  
Arie Erman ◽  
Larisa Bachmetov ◽  
...  
Keyword(s):  
Vitamin D ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Vitamin D Receptor ◽  
Vitamin D3 ◽  
Mode Of Action ◽  
Virus Production ◽  
Independent Manner ◽  
Hydroxyvitamin D ◽  
Independent Mechanism

Previously, we have reported that the active vitamin D metabolite, calcitriol and vitamin D3 (cholecalciferol), both remarkably inhibit hepatitis C virus production. The mechanism by which vitamin D3 exerts its effect is puzzling due to the low levels of calcitriol produced in vitamin D3-treated Huh7.5 cells. In this study, we aimed to explore the mechanism of vitamin D3 anti-hepatitis C virus effect. We show that vitamin D3 activity is not mediated by its metabolic conversion to calcitriol, but may be due to its primary metabolic product 25(OH)D3. This is inferred from the findings that 25(OH)D3 could inhibit hepatitis C virus production in our system, and that adequate concentrations needed to exert this effect are produced in Huh7.5 cells treated with vitamin D3. Using the CRISPR-Cas9 editing technology to knockout the vitamin D receptor, we found that the antiviral activity of vitamin D3 and 25(OH)D3 was not impaired in the vitamin D receptor knockout cells. This result indicates that 25(OH)D3 anti-hepatitis C virus effect is exerted by a vitamin D receptor-independent mode of action. The possibility that vitamin D3 and 25(OH)D3, being 3β-hydroxysteroids, affect hepatitis C virus production by direct inhibition of the Hedgehog pathway in a vitamin D receptor-independent manner was ruled out. Taken together, this study proposes a novel mode of action for the anti-hepatitis C virus activity of vitamin D3 that is mediated by 25(OH)D3 in a vitamin D receptor-independent mechanism.

scholarly journals Vitamin D receptor–mediated skewed differentiation of macrophages initiates myelofibrosis and subsequent osteosclerosis

Blood ◽  
2019 ◽  
Vol 133 (15) ◽  
pp. 1619-1629 ◽  
Author(s):  
Kanako Wakahashi ◽  
Kentaro Minagawa ◽  
Yuko Kawano ◽  
Hiroki Kawano ◽  
Tomohide Suzuki ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Transforming Growth Factor ◽  
Myeloproliferative Neoplasms ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β1 ◽  
Independent Manner ◽  
Hematopoietic Stem ◽  
Macrophage Depletion ◽  
Donor Cells

Abstract Myelofibrosis in myeloproliferative neoplasms (MPNs) with mutations such as JAK2V617F is an unfavorable sign for uncontrollable disease progression in the clinic and is complicated with osteosclerosis whose pathogenesis is largely unknown. Because several studies have revealed that macrophages are an indispensable supporter for bone-forming osteoblasts, we speculated that macrophages might play a significant role in the proliferation of collagen-producing myofibroblasts in marrow fibrotic tissues. Here, we show that myelofibrosis critically depends on macrophages whose differentiation is skewed by vitamin D receptor (VDR) signaling. In our novel myelofibrosis model established by transplantation of VDR+/+ hematopoietic stem/progenitor cells into VDR−/− mice, donor-derived F4/80+ macrophages proliferated together with recipient-derived α-smooth muscle actin–positive myofibroblasts, both of which comprised fibrotic tissues with an indistinguishable spindle-shaped morphology. Interfering VDR signals, such as low vitamin D diet and VDR deficiency in donor cells as well as macrophage depletion prevented myelofibrosis in this model. These interventions also ameliorated myelofibrosis in JAK2V617F-driven murine MPNs likely in a transforming growth factor-β1– or megakaryocyte-independent manner. These results suggest that VDR and macrophages may be novel therapeutic targets for MPNs with myelofibrosis.

The CDX2-site polymorphism in the vitamin D receptor gene and expression of genes for intestinal calcium absorption

2003 ◽  
Vol 124 (4) ◽  
pp. A126
Author(s):  
Julian R. Walters ◽  
Mohammed Khanji ◽  
Natalie Barley ◽  
Orli Rhodes-Kendler ◽  
Umma Khair
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Calcium Absorption ◽  
Receptor Gene ◽  
Intestinal Calcium Absorption ◽  
Vitamin D Receptor Gene ◽  
Expression Of Genes

scholarly journals Pregnancy Up-Regulates Intestinal Calcium Absorption and Skeletal Mineralization Independently of the Vitamin D Receptor

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 886-895 ◽  
Author(s):  
Neva J. Fudge ◽  
Christopher S. Kovacs
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Calcium Absorption ◽  
Fold Increase ◽  
Normal Diet ◽  
Intestinal Calcium Absorption ◽  
A Genome ◽  
Pregnancy And Lactation ◽  
Turnover Markers ◽  
Calbindin D

Without the vitamin D receptor (VDR), adult mammals develop reduced intestinal calcium absorption, rickets, and osteomalacia. Intestinal calcium absorption normally increases during pregnancy so that the mother can supply sufficient calcium to her fetuses. The maternal skeleton is rapidly resorbed during lactation to provide calcium needed for milk; that lost bone mineral content (BMC) is completely restored after weaning. We studied Vdr null mice to determine whether these adaptations during pregnancy and lactation require the VDR. Vdr nulls were severely rachitic at 10 wk of age on a normal diet. Pregnancy induced a 158% increase in Vdr null BMC to equal the pregnant wild-type (WT) value. Lactation caused BMC losses that were equal in Vdr nulls and WT. Vdr nulls recovered after weaning to a BMC 50% higher than before pregnancy and equal to WT. Additional analyses showed that during pregnancy, duodenal 45Ca absorption increased in Vdr nulls, secondary hyperparathyroidism lessened, bone turnover markers decreased, and osteoid became fully mineralized. A genome-wide microarray analysis of duodenal RNA found marked reduction of Trpv6 in Vdr nulls at baseline but a 13.5-fold increase during pregnancy. Calbindin D-9K (S100g) and Ca2+-ATPase (Pmca1) were not altered by pregnancy. Several other solute transporters increased during pregnancy in Vdr nulls. In summary, Vdr nulls adapt to pregnancy by up-regulating duodenal Trpv6 and intestinal 45Ca absorption, thereby enabling rapid normalization of BMC during pregnancy. These mice lactate normally and fully restore BMC after weaning. Therefore, VDR is not required for the skeletal adaptations during pregnancy, lactation, and after weaning.

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