scholarly journals Vitamin D Receptor Protects against Radiation-Induced Intestinal Injury in Mice via Inhibition of Intestinal Crypt Stem/Progenitor Cell Apoptosis

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2910
Author(s):  
Wusun Li ◽  
Yingying Lin ◽  
Yujia Luo ◽  
Yuqi Wang ◽  
Yao Lu ◽  
...  
Keyword(s):  
Vitamin D ◽  
Dna Damage ◽  
Radiation Therapy ◽  
Vitamin D Receptor ◽  
Cell Apoptosis ◽  
Progenitor Cell ◽  
Intestinal Injury ◽  
Apoptotic Pathway ◽  
Intestinal Crypt

It is urgent to seek new potential targets for the prevention or relief of gastrointestinal syndrome in clinical radiation therapy for cancers. Vitamin D, mediated through the vitamin D receptor (VDR), has been identified as a protective nutrient against ionizing radiation (IR)-induced damage. This study investigated whether VDR could inhibit IR-induced intestinal injury and explored underlying mechanism. We first found that vitamin D induced VDR expression and inhibited IR-induced DNA damage and apoptosis in vitro. VDR was highly expressed in intestinal crypts and was critical for crypt stem/progenitor cell proliferation under physiological conditions. Next, VDR-deficient mice exposed to IR significantly increased DNA damage and crypt stem/progenitor cell apoptosis, leading to impaired intestinal regeneration as well as shorter survival time. Furthermore, VDR deficiency activated the Pmaip1-mediated apoptotic pathway of intestinal crypt stem/progenitor cells in IR-treated mice, whereas inhibition of Pmaip1 expression by siRNA transfection protected against IR-induced cell apoptosis. Therefore, VDR protects against IR-induced intestinal injury through inhibition of crypt stem/progenitor cell apoptosis via the Pmaip1-mediated pathway. Our results reveal the importance of VDR level in clinical radiation therapy, and targeting VDR may be a useful strategy for treatment of gastrointestinal syndrome.

scholarly journals Vitamin D receptor expression in SLE peripheral blood CD4+T cells is associated with disease activity and cell apoptosis

2021 ◽  
Author(s):  
Ying Zhang ◽  
Lingying Niu ◽  
Fan Wang ◽  
Xiaojun Tang ◽  
Chun Wang ◽  
...  
Keyword(s):  
Vitamin D ◽  
T Cells ◽  
Disease Activity ◽  
Vitamin D Receptor ◽  
Cell Apoptosis ◽  
Cd4 T Cells ◽  
Activity Index ◽  
Receptor Expression ◽  
Th2 Cells ◽  
Tfh Cells

ABSTRACT Objectives Systemic lupus erythematosus (SLE) is characterised by accumulated cell apoptosis. Vitamin D receptor (VDR) has immunomodulatory effect and potent anti-apoptosis activities. The aim of this study was to examine the correlation between CD4+T cells VDR expression, cell apoptosis, and disease activity in patients with SLE. Methods Forty-five SLE patients were recruited and 50 healthy individuals served as controls. The expression of VDR in CD4+T cells and their subsets were determined by flow cytometry. The correlations between VDR expression and cell apoptosis or disease parameters in SLE patients were analysed. Results VDR expression in CD4+T cells and their subsets were upregulated in SLE patients, especially in help T (Th)1, regulatory T (Treg), and follicular helper T (Tfh) cells. Frequency of VDR-positive CD4+T cells was positively associated with SLE disease activity index (SLEDAI)-2K values and inversely correlated with serum C3 concentration. The frequency of VDR-positive CD4+T cells, Th1 cells, Th2 cells, Th17 cells, Treg cells, and Tfh cells was positively correlated with cells apoptosis. Conclusion VDR expression in CD4+T cells and their subsets were increased in SLE. VDR expression was positively associated with disease activity and cell apoptosis in SLE patients.

scholarly journals 1,25-Dihydroxy-19-nor-vitamin D2, a Vitamin D Analog with Reduced Bone Resorbing Activity In Vitro

2000 ◽  
Vol 11 (10) ◽  
pp. 1857-1864
Author(s):  
L. SHANNON HOLLIDAY ◽  
STEPHEN L. GLUCK ◽  
EDUARDO SLATOPOLSKY ◽  
ALEX J. BROWN
Keyword(s):  
Vitamin D ◽  
Acid Phosphatase ◽  
Bone Resorption ◽  
Vitamin D Receptor ◽  
Intrinsic Activity ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mouse Bone Marrow ◽  
Bone Resorbing Activity

Abstract. 1,25-Dihydroxy-19-nor-vitamin D2 (19-norD2), a new analog of 1,25(OH)2D3, suppresses parathyroid hormone in renal failure patients and in uremic rats but has less calcemic activity than 1,25(OH)2D3. Although 19-norD2 has high affinity for the vitamin D receptor and similar pharmacokinetics to those of 1,25(OH)2D3, it has much less bone resorbing activity in vivo. The intrinsic activity of 19-norD2 on osteoclastogenesis and activation of bone resorption in mouse bone marrow cultures was examined to determine the mechanism involved. 19-norD2 and 1,25(OH)2D3 (10 nM) were equivalent in stimulating the formation and maintenance of large multinucleated, tartrate-resistant acid phosphatase-positive cells. However, the amount of bone resorbed by osteoclasts stimulated by 10 nM 19-norD2, as measured by pit-forming assays, was reduced 62% compared with 10 nM 1,25(OH)2D3-stimulated osteoclasts (P < 0.05). This difference could not be attributed to enhanced catabolism or to downregulated vitamin D receptor. The rate of degradation of 19-norD2 in cultures was approximately 20% greater than 1,25(OH)2D3, not enough to account for the different effects on bone resorption. The VDR levels were identical in cultures that were treated with 19-norD2 and 1,25(OH)2D3. In summary, 19-norD2 is less effective than 1,25(OH)2D3 in stimulating mouse marrow osteoclasts to resorb bone. The reason for this difference is not clear but seems to involve the late maturation and/or activation of osteoclasts as the number of pits produced by each tartrate-resistant acid phosphatase-positive cell is reduced under stimulation by 19-norD2 compared with 1,25(OH)2D3.

scholarly journals The vitamin D receptor regulates mitochondrial function in C2C12 myoblasts

2020 ◽  
Vol 318 (3) ◽  
pp. C536-C541 ◽  
Author(s):  
Stephen P. Ashcroft ◽  
Joseph J. Bass ◽  
Abid A. Kazi ◽  
Philip J. Atherton ◽  
Andrew Philp
Keyword(s):  
Skeletal Muscle ◽  
Vitamin D ◽  
Protein Content ◽  
Vitamin D Receptor ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Oxidative Capacity ◽  
C2c12 Myoblasts

Vitamin D deficiency has been linked to a reduction in skeletal muscle function and oxidative capacity; however, the mechanistic bases of these impairments are poorly understood. The biological actions of vitamin D are carried out via the binding of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) to the vitamin D receptor (VDR). Recent evidence has linked 1α,25(OH)2D3 to the regulation of skeletal muscle mitochondrial function in vitro; however, little is known with regard to the role of the VDR in this process. To examine the regulatory role of the VDR in skeletal muscle mitochondrial function, we used lentivirus-mediated shRNA silencing of the VDR in C2C12 myoblasts (VDR-KD) and examined mitochondrial respiration and protein content compared with an shRNA scrambled control. VDR protein content was reduced by ~95% in myoblasts and myotubes ( P < 0.001). VDR-KD myoblasts displayed a 30%, 30%, and 36% reduction in basal, coupled, and maximal respiration, respectively ( P < 0.05). This phenotype was maintained in VDR-KD myotubes, displaying a 34%, 33%, and 48% reduction in basal, coupled, and maximal respiration ( P < 0.05). Furthermore, ATP production derived from oxidative phosphorylation (ATPOx) was reduced by 20%, suggesting intrinsic impairments within the mitochondria following VDR-KD. However, despite the observed functional decrements, mitochondrial protein content, as well as markers of mitochondrial fission were unchanged. In summary, we highlight a direct role for the VDR in regulating skeletal muscle mitochondrial respiration in vitro, providing a potential mechanism as to how vitamin D deficiency might impact upon skeletal muscle oxidative capacity.

Is the natural PCDD/PCDF mixture toxic for human placental JEG-3 cell line? The action of the toxicants on hormonal profile, CYP1A1 activity, DNA damage and cell apoptosis

2007 ◽  
Vol 26 (5) ◽  
pp. 407-417 ◽  
Author(s):  
Katarzyna Augustowska ◽  
Zofia Magnowska ◽  
Maria Kapiszewska ◽  
Ewa L. Gregoraszczuk
Keyword(s):  
Dna Damage ◽  
Cell Line ◽  
Cell Apoptosis ◽  
Hormone Production ◽  
Dna Migration ◽  
Extraction And Purification ◽  
Cyp1a1 Expression ◽  
Cross Links ◽  
Placental Hormone

The present study was conducted to define the action of a mixture obtained by the extraction and purification of real fly ash, on specific toxicity endpoints, such as hormonal secretion, CYP1A1 expression, DNA damage and cell apoptosis. JEG-3 cell line was exposed in vitro to different doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or Polychlorinated dibenzo-p-dioxin/Polychlorinated dibenzo-P-furan (PCDD/PCDF) mixture. Both TCDD and the mixture decreased hCG secretion, while inhibition of progesterone levels was noted only under the influence of TCDD. The changes in hormone production were not due to the action on cell viability. There were time-dependent differences in CYP1A1 expression in cells exposed to TCDD and PCDD/PCDF mixture. Both TCDD and PCDD/PCDF mixture did not induce the DNA damage, as evaluated by the comet assay. Significantly lower DNA migration from the head of comet into the comet tail was noted after the removal of reagents. The highest efficiency of this process was noted 4 h after the TCDD and 24 h after the PCDD/PCDF mixture removal. These results suggest that the DNA adducts and/or DNA—DNA cross-links were formed. Neither TCDD nor PCDD/PCDF mixture had any effect on cell apoptosis assessed by caspase-3 activity and Hoechst 33258. Taken together, these findings clearly indicate a weaker action of the mixture when compared with TCDD. However, in both cases, their action was not due to the induction of the DNA damage and subsequent cell apoptosis but due to a direct influence of these toxicants on placental hormone production. Human & Experimental Toxicology ( 2007) 26, 407—417

scholarly journals Parathyroid hormone prevents 1,25(OH)2D3 induced down-regulation of the vitamin D receptor in growth plate chondrocytes in vitro

1997 ◽  
Vol 52 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Günter Klaus ◽  
Tanja May ◽  
Ulrike Hügel ◽  
Barbara Von Eichel ◽  
Julian Rodriguez ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Growth Plate ◽  
Vitamin D Receptor ◽  
Growth Plate Chondrocytes ◽  
Down Regulation

scholarly journals Prominent Levels of the Profibrotic Chemokine CCL18 during Peritonitis: In Vitro Downregulation by Vitamin D Receptor Agonists

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Marta Ossorio ◽  
Virginia Martínez ◽  
Maria-Auxiliadora Bajo ◽  
Gloria Del Peso ◽  
Maria-José Castro ◽  
...  
Keyword(s):  
Vitamin D ◽  
Risk Factor ◽  
Vitamin D Receptor ◽  
Peritoneal Macrophages ◽  
Peritoneal Membrane ◽  
Pharmacological Interventions ◽  
Membrane Function ◽  
Bacterial Peritonitis ◽  
Ultrafiltration Failure

Peritoneal dialysis (PD) is used as a renal replacement therapy, which can be limited by peritoneal membrane ultrafiltration failure (UFF) secondary to fibrotic processes. Peritonitis, a frequent complication of PD, is a major risk factor for peritoneal membrane fibrosis and UFF. Low peritoneal levels of the chemokine CCL18 are associated with preservation of peritoneal membrane function in PD. Given that CCL18 is involved in fibrotic processes and recurrent peritonitis, it is a risk factor for peritoneal membrane failure; thus, we evaluated CCL18 concentrations in peritoneal effluents from patients undergoing peritonitis episodes. Pharmacological interventions aimed at diminishing the production of CCL18 were also explored. Fivefold higher CCL18 peritoneal concentrations were found during acute bacterial peritonitis, in parallel with the increased infiltration of macrophages. Unexpectedly, CCL18 was also highly (50-fold) increased during sterile eosinophilic peritonitis, and peritoneal eosinophils were found to express CCL18. In vitro treatment of peritoneal macrophages with the vitamin D receptor agonist paricalcitol was able to reduce the secretion and the expression of CCL18 in isolated peritoneal macrophages. In conclusion, our study suggests that the chemokine CCL18 can be a mediator of peritoneal membrane failure associated with peritonitis episodes as well as providing a new potential therapeutic target.

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