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. 2016 Sep;23(3):155-161.
doi: 10.1159/000449181. Epub 2016 Sep 9.

The Three Sisters of Fate in Multiple Sclerosis: Klotho (Clotho), Fibroblast Growth Factor-23 (Lachesis), and Vitamin D (Atropos)

Hamit Yasar Ellidag  1 , Necat Yilmaz  1 , Fatma Kurtulus  2 , Ozgur Aydin  3 , Esin Eren  1 , Ayca Inci  4 , Suleyman Dolu  4 , Fatma Demet Arslan Ince  5 , Özlem Giray  1 , Aylin Yaman  2
Affiliations

The Three Sisters of Fate in Multiple Sclerosis: Klotho (Clotho), Fibroblast Growth Factor-23 (Lachesis), and Vitamin D (Atropos)

Hamit Yasar Ellidag et al. Ann Neurosci. 2016 Sep.

Abstract

Background: The klotho (Klt)-fibroblast growth factor-23 (FGF-23)-vitamin D axis is the main component of calcium (Ca) and phosphorus (P) metabolisms; on the contrary, it is also secreted from the choroid plexus (CP).

Purpose: This study is aimed at evaluating serum soluble Klt (sKlt), FGF-23, and 25-(OH)-vitamin D levels in multiple sclerosis (MS) patients.

Methods: Thirty-two relapsing-remitting MS patients (11 males and 21 females; mean age 38.3 years) and 31 age-sex matched healthy controls (12 males and 19 females; median age 38.5 years) were included in this study. All patients were diagnosed with MS according to the criteria of McDonald.

Results: Serum sKlt, FGF-23, and P levels were significantly higher in MS patients compared to the control group (p < 0.01, p < 0.01, and p = 0.02, respectively). Serum 25-(OH)-vitamin D and Ca levels were significantly lower in MS patients (p < 0.01 and p = 0.04, respectively).

Conclusion: Klt, which is secreted from CP, could be a response to the inflammatory condition in MS. Elevated FGF-23 levels suppress 1α-hydroxylase and upregulates 24α-hydroxylase, which results in a decrease in 1,25-(OH)2D3 levels. Thus, the neuroprotective and immunomodulatory effects of vitamin D might not be seen in MS patients.

Keywords: Choroid plexus; Demyelinization; Fibroblast growth factor-23; Klotho; Multiple sclerosis; Oligodendrocyte; Vitamin D.

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Figures

Fig. 1
Fig. 1
The levels of sKlt, FGF-23 and 25-(OH)-vitamin D in MS patients and controls. Serum sKlt and FGF-23 levels were significantly higher in patients with MS than in controls, whereas 25-(OH)-vitamin D levels were significantly lower in MS patients.
Fig. 2
Fig. 2
A vicious cycle of KL/FGF-23/vitamin D axis in MS patients.
See this image and copyright information in PMC

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