1.
Mechanisms of action of vitamin D in colon cancer.
Ferrer-Mayorga, G, Larriba, MJ, Crespo, P, Muñoz, A
The Journal of steroid biochemistry and molecular biology. 2019;:1-6
-
-
Free full text
-
Abstract
Colorectal cancer (CRC) is the neoplasia that is most frequently associated with vitamin D deficiency in epidemiological and observational studies in terms of incidence and mortality. Many mechanistic studies show that the active vitamin D metabolite (1α,25-dihydroxyvitamin D3 or calcitriol) inhibits proliferation and promotes epithelial differentiation of human colon carcinoma cell lines that express vitamin D receptor (VDR) via the regulation of a high number of genes. A key action underlining this effect is the multilevel inhibition of the Wnt/β-catenin signaling pathway, whose abnormal activation in colon epithelial cells initiates and promotes CRC. Recently, our group has shown that calcitriol modulates gene expression and inhibits protumoral properties of patient-derived colon cancer-associated fibroblasts (CAFs). Accordingly, high VDR expression in tumor stromal fibroblasts is associated with longer survival of CRC patients. Moreover, many types of immune cells express VDR and are regulated by calcitriol, which probably contributes to its action against CRC. Given the role attributed to the intestinal microbiota in CRC and the finding that it is altered by vitamin D deficiency, an indirect antitumoral effect of calcitriol is also plausible at this level. In summary, calcitriol has an array of potential protective effects against CRC by acting on carcinoma cells, CAFs, immune cells and probably also the gut microbiota.
2.
[Rickets/Osteomalacia. The function and mechanism of vitamin D action.].
Makishima, M
Clinical calcium. 2018;(10):1319-1326
Abstract
The antirickets factor vitamin D exhibits its action through activation of vitamin D receptor(VDR). The active form of vitamin D, 1α,25-dihydroxyvitamin D3[1,25(OH)2D3], is a potent VDR ligand, and contributes to the maintenance of calcium homeostasis by enhancing intestinal calcium absorption, renal calcium reabsorption and bone resorption. 1,25(OH)2D3 also regulates bone formation, phosphorus metabolism and vitamin D metabolism. Experimental and epidemiological evidence has shown vitamin D actions on cellular proliferation and differentiation, immunity and inflammation, and cardiovascular function. Vitamin D derivatives and VDR ligands may be useful for the treatment of osteoporosis, malignancy, autoimmune and inflammatory disease and cardiovascular disease as well as rickets and osteomalacia.
3.
Vitamin D: Classic and Novel Actions.
Gil, Á, Plaza-Diaz, J, Mesa, MD
Annals of nutrition & metabolism. 2018;(2):87-95
-
-
Free full text
-
Abstract
BACKGROUND Classically, vitamin D has been implicated in bone health by promoting calcium absorption in the gut and maintenance of serum calcium and phosphate concentrations, as well as by its action on bone growth and reorganization through the action of osteoblasts and osteoclasts cells. However, in the last 2 decades, novel actions of vitamin D have been discovered. The present report summarizes both classic and novel actions of vitamin D. SUMMARY 1,25(OH)2 vitamin D, the active metabolite of vitamin D, also known as calcitriol, regulates not only calcium and phosphate homeostasis but also cell proliferation and differentiation, and has a key a role to play in the responses of the immune and nervous systems. Current effects of vitamin D include xenobiotic detoxification, oxidative stress reduction, neuroprotective functions, antimicrobial defense, immunoregulation, anti-inflammatory/anticancer actions, and cardiovascular benefits. The mechanism of action of calcitriol is mediated by the vitamin D receptor, a subfamily of nuclear receptors that act as transcription factors into the target cells after forming a heterodimer with the retinoid X receptor. This kind of receptors has been found in virtually all cell types, which may explain its multiple actions on different tissues. Key Messages: In addition to classic actions related to mineral homeostasis, vitamin D has novel actions in cell proliferation and differentiation, regulation of the innate and adaptative immune systems, preventive effects on cardiovascular and neurodegenerative diseases, and even antiaging effects.
4.
The D-vitamin metabolite 1,25(OH)2 D in serum is associated with disease activity and Anti-Citrullinated Protein Antibodies in active and treatment naïve, early Rheumatoid Arthritis Patients.
Herly, M, Stengaard-Pedersen, K, Vestergaard, P, Østergaard, M, Junker, P, Hetland, ML, Hørslev-Petersen, K, Ellingsen, T
Scandinavian journal of immunology. 2018;(3):e12704
Abstract
RATIONALE Sufficient levels of vitamin D seem to be essential for proper immune function, and low levels might be associated to disease activity in Rheumatoid Arthritis (RA). Most studies investigate only 25OHD and not the physiologically active vitamin D metabolite, 1,25(OH)2 D. OBJECTIVE To investigate associations between serum level of vitamin D metabolites and disease activity parameters in 160 inflammatory active and treatment naïve early RA patients. Serum level of vitamin D metabolites (25OHD2 , 25OHD3 and 1,25(OH)2 D) was measured by isotope dilution mass spectrometry and radio-immunoassays at baseline. Disease characteristics were gender, number of tender joints, number of swollen joints, DAS28-CRP, HAQ, VAS-scores, CRP, erosive status (Total Sharp Score; TSS), ACPA and IgM-RF-status. Associations were evaluated using Spearman's and Wilcoxon rank-sum tests. The study was registered in clinical trials; trial registration number: NCT00209859. FINDINGS Statistically significant inverse associations were found between the active metabolite 1,25(OH)2 D and DAS28-CRP (P = 0.004, rho = -0.23), HAQ (P = 0.005, rho = -0.22), CRP (P = 0.001, rho = -0.25), VASpatient-pain (P = 0.008, rho = -0.21), and a positive association was found to ACPA-status (P = 0.04). CONCLUSION The vitamin D metabolite 1,25(OH)2 D was inversely associated with disease activity and positively associated with ACPA in treatment naïve and inflammatory active early RA. The results indicate that in RA, both the degree of inflammatory activity, and the diagnostic sensitivity and specificity might affect-or might be affected by the level of vitamin 1,25(OH)2 D.
5.
Vitamin D-binding protein as it is understood in 2016: is it a critical key with which to help to solve the calcitriol conundrum?
Davey, RX
Annals of clinical biochemistry. 2017;(2):199-208
Abstract
Background The misnamed 'vitamin' D is actually the hormone calcitriol (1,25 dihydroxyhydroxyvitamin D). It has a central regulatory role in calcium metabolism, and more widely in the immune system. The prohormone calcifediol (25 hydroxyvitamin D) is more easily measured in the laboratory and is the analyte used in reference interval formulation. Being highly lipid soluble, both calcifediol and calcitriol travel in the bloodstream on carriage proteins, principally on vitamin D-binding protein. Summary This review reports our current understanding of vitamin D-binding protein. Its genetic determinants and their effect on it and secondarily on calcifediol concentrations and assays are described. Its complex interplay with parathyroid hormone is considered. The analytical state of the art is translated into the challenge it imposes clinically, in the formulation of reference intervals and in their use in advising and managing patients. Several recent challenges thrown up to laboratories by percipient clinicians highlight the dilemma vitamin D-binding protein poses. A way forward is suggested.