Central role of the proximal tubular αKlotho/FGF receptor complex in FGF23-regulated phosphate and vitamin D metabolism

Fat tissue represents an important source of adipose-derived stem cells (ADSCs), which can differentiate towards several phenotypes under certain stimuli. Definite molecules as vitamin D are able to influence stem cell fate, acting on the expression of specific genes. In addition, miRNAs are important modulating factors in obesity and numerous diseases. We previously identified specific conditioned media able to commit stem cells towards defined cellular phenotypes. In the present paper, we aimed at evaluating the role of metformin on ADSCs differentiation. In particular, ADSCs were cultured in a specific adipogenic conditioned medium (MD), in the presence of metformin, alone or in combination with vitamin D. Our results showed that the combination of the two compounds is able to counteract the appearance of an adipogenic phenotype, indicating a feedforward regulation on vitamin D metabolism by metformin, acting on CYP27B1 and CYP3A4. We then evaluated the role of specific epigenetic modulating genes and miRNAs in controlling stem cell adipogenesis. The combination of the two molecules was able to influence stem cell fate, by modulating the adipogenic phenotype, suggesting their possible application in clinical practice in counteracting uncontrolled lipogenesis and obesity-related diseases.

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Investigation of the role of vitamin D metabolism in South African breast cancer patients using whole exome sequencing

The Breast ◽

10.1016/s0960-9776(19)30162-6 ◽

2019 ◽

Vol 44 ◽

pp. S36

Author(s):

A. Okunola ◽

R. Torrorey-Sawe ◽

K.J. Baatjes ◽

A.E. Zemlin ◽

R.T. Erasmus ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Exome Sequencing ◽

Cancer Patients ◽

South African ◽

Whole Exome Sequencing ◽

Breast Cancer Patients ◽

Vitamin D Metabolism ◽

Whole Exome

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Vitamin D and prostate cancer

Medicinski pregled ◽

10.2298/mpns1306259m ◽

2013 ◽

Vol 66 (5-6) ◽

pp. 259-262

Author(s):

Goran Marusic ◽

Dimitrije Jeremic ◽

Sasa Vojinov ◽

Natasa Filipovic ◽

Milan Popov

Keyword(s):

Prostate Cancer ◽

Vitamin D ◽

Physiological Role ◽

In Vivo Studies ◽

Vitamin D Metabolism ◽

Genetic Changes ◽

Metabolic Role

In addition to the metabolic role of vitamin D, which is well known and clearly defined, there have been many hypotheses regarding its anti-proliferative and pro-apoptotic role. Epidemiology and Significance of Prostate Cancer. Prostate cancer is the second most common malignancy in men. Long period of cancerogenesis, available tumor markers and high incidence make this cancer ideal for preventive measures. Physiological Role of Vitamin D and its Effect on Prostate Cancer Cells. In vitro and in vivo studies have shown the anti-proliferative and pro-apoptopic role of vitamin D. Disorders of vitamin D metabolism are noted in vitamin D gene level, vitamin D receptor, vitamin D responsive elements and androgen receptors. We present the most important effect of those changes on vitamin D metabolism. Conclusion. Available studies on vitamin D level in serum, prostate tissue, observed activity of vitamin D enzymes and genetic changes give us only a slight insight into the basic mechanisms of vitamin D action in the development of prostate cancer; therefore, further investigations are needed.

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Clinical Significance of FGF-23 in Patients with CKD

International Journal of Nephrology ◽

10.4061/2011/364890 ◽

2011 ◽

Vol 2011 ◽

pp. 1-5 ◽

Cited By ~ 20

Author(s):

Domenico Russo ◽

Yuri Battaglia

Keyword(s):

Ventricular Hypertrophy ◽

Vascular Dysfunction ◽

Left Ventricular ◽

Vitamin D Metabolism ◽

Fgf Receptor ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Phosphate Retention ◽

Fgf 23

FGF23 is a bone-derived hormone that plays an important role in the regulation of phosphate and 1,25-dihydroxy vitamin D metabolism. FGF23 principally acts in the kidney to induce urinary phosphate excretion and suppress 1,25-dihydroxyvitamin D synthesis in the presence of FGF receptor 1 (FGFR1) and its coreceptor Klotho. In patients with chronic kidney disease (CKD), circulating FGF23 levels are progressively increased to compensate for persistent phosphate retention, but this results in reduced renal production of 1,25-dihydroxyvitamin D and leads to hypersecretion of parathyroid hormone. Furthermore, FGF23 is associated with vascular dysfunction, atherosclerosis, and left ventricular hypertrophy. This paper summarizes the role of FGF23 in the pathogenesis of mineral, bone, and cadiovascular disorders in CKD.

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Role of prolactin in vitamin D metabolism and calcium absorption during lactation in the rat

Journal of Endocrinology ◽

10.1677/joe.0.0940443 ◽

1982 ◽

Vol 94 (3) ◽

pp. 443-453 ◽

Cited By ~ 53

Author(s):

C. J. Robinson ◽

E. Spanos ◽

M. F. James ◽

J. W. Pike ◽

M. R. Haussler ◽

...

Keyword(s):

Vitamin D ◽

Alkaline Phosphatase ◽

Parathyroid Hormone ◽

Alkaline Phosphatase Activity ◽

Plasma Levels ◽

Calcium Absorption ◽

High Plasma ◽

Intestinal Calcium Absorption ◽

Vitamin D Metabolism

Intestinal calcium absorption and plasma levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) were measured in lactating and non-lactating rats and the effects of bromocriptine and exogenous prolactin treatment were evaluated. In lactating rats calcium absorption and plasma levels of parathyroid hormone, 1,25(OH)2D3 and alkaline phosphatase activity were significantly increased. Bromocriptine treatment significantly reduced the enhanced calcium absorption and levels of plasma 1,25(OH)2D3 and alkaline phosphatase but had no significant effect on plasma levels of parathyroid hormone. Prolactin administered with bromocriptine to lactating animals prevented all the changes observed with bromocriptine treatment alone. It was concluded that the increased plasma levels of prolactin during lactation lead to high plasma levels of 1,25(OH)2D3 which are responsible for the enhanced intestinal calcium absorption.

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Role of the vitamin D receptor in FGF23 action on phosphate metabolism

Biochemical Journal ◽

10.1042/bj20041799 ◽

2005 ◽

Vol 390 (1) ◽

pp. 325-331 ◽

Cited By ~ 127

Author(s):

Yoshio Inoue ◽

Hiroko Segawa ◽

Ichiro Kaneko ◽

Setsuko Yamanaka ◽

Kenichiro Kusano ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Receptor ◽

Fibroblast Growth Factor 23 ◽

Mrna Levels ◽

Dna Encoding ◽

Vitamin D Metabolism ◽

Hydroxyvitamin D ◽

Naked Dna ◽

25 Hydroxyvitamin D

FGF23 (fibroblast growth factor 23) is a novel phosphaturic factor that influences vitamin D metabolism and renal re-absorption of Pi. The goal of the present study was to characterize the role of the VDR (vitamin D receptor) in FGF23 action using VDR(−/−) (VDR null) mice. Injection of FGF23M (naked DNA encoding the R179Q mutant of human FGF23) into VDR(−/−) and wildtype VDR(+/+) mice resulted in an elevation in serum FGF23 levels, but had no effect on serum calcium or parathyroid hormone levels. In contrast, injection of FGF23M resulted in significant decreases in serum Pi levels, renal Na/Pi co-transport activity and type II transporter protein levels in both groups when compared with controls injected with mock vector or with FGFWT (naked DNA encoding wild-type human FGF23). Injection of FGF23M resulted in a decrease in 25-hydroxyvitamin D 1α-hydroxylase mRNA levels in VDR(−/−) and VDR(+/+) mice, while 25-hydroxyvitamin D 24-hydroxylase mRNA levels were significantly increased in FGF23M-treated animals compared with mock vector control- or FGF23WT-treated animals. The degree of 24-hydroxylase induction by FGF23M was dependent on the VDR, since FGF23M significantly reduced the levels of serum 1,25(OH)2D3 [1,25-hydroxyvitamin D3] in VDR(+/+) mice, but not in VDR(−/−) mice. We conclude that FGF23 reduces renal Pi transport and 25-hydroxyvitamin D 1α-hydroxylase levels by a mechanism that is independent of the VDR. In contrast, the induction of 25-hydroxyvitamin D 24-hydroxylase and the reduction of serum 1,25(OH)2D3 levels induced by FGF23 are dependent on the VDR.

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