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Vitamin D inhibits lymphangiogenesis through VDR-dependent mechanisms

Yazdani, S., Poosti, F., Toro, L., Wedel, J., Mencke, R., Mirkovic, K., de Borst, M. H., Alexander, J. S., Navis, G., van Goor, H., van den Born, J. & Hillebrands, J-L. 7-Feb-2017 In : Scientific Reports. 26 p.

Research output: Scientific - peer-reviewArticle

Excessive lymphangiogenesis is associated with cancer progression and renal disease.
Attenuation of lymphangiogenesis might represent a novel strategy to target disease progression
although clinically approved anti-lymphangiogenic drugs are not available yet. VitaminD(VitD)-
deficiency is associated with increased cancer risk and chronic kidney disease. Presently, effects
of VitD on lymphangiogenesis are unknown. Given the apparently protective effects of VitD and
the deleterious associations of lymphangiogenesis with renal disease, we here tested the
hypothesis that VitD has direct anti-lymphangiogenic effects in vitro and is able to attenuate
lymphangiogenesis in vivo. In vitro cultured mouse lymphatic endothelial cells (LECs) expressed
VitD Receptor (VDR), both on mRNA and protein levels. Active VitD (calcitriol) blocked LEC
tube formation, reduced LEC proliferation, and induced LEC apoptosis. siRNA-mediated VDR
knock-down reversed the inhibitory effect of calcitriol on LEC tube formation, demonstrating
how such inhibition is VDR-dependent. In vivo, proteinuric rats were treated with vehicle or
paricalcitol for 6 consecutive weeks. Compared with vehicle-treated proteinuric rats, paricalcitol
showed markedly reduced renal lymphangiogenesis. In conclusion, our data show that VitD is
anti-lymphangiogenic through VDR-dependent anti-proliferative and pro-apoptotic mechanisms.
Our findings highlight an important novel function of VitD demonstrating how it may have
therapeutic value in diseases accompanied by pathological lymphangiogenesis.
Original languageEnglish
Number of pages26
JournalScientific Reports
StateAccepted/In press - 7-Feb-2017

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