25-Hydroxyvitamin D3-1α-hydroxylase is expressed in human vascular smooth muscle cells and is upregulated by parathyroid hormone and estrogenic compounds

Dalia Somjen, Yosef Weisman, Fortune Kohen, Batya Gayer, Rona Limor, Orly Sharon, Niva Jaccard, Esther Knoll, Naftali Stern*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background - 1,25(OH)2 vitamin D3 exerts multiple effects in human vascular smooth muscle cells (VSMCs). We therefore tested the possibility that VSMCs possess an endogenous 25-hydroxyvitamin D 3-1α-hydroxylase system, the final enzyme in the biosynthetic pathway of 1,25(OH)2D3. Methods and Results - We assessed the expression and activity of 25-hydroxyvitamin D3-1α- hydroxylase by real-time polymerase chain reaction and the conversion of 25(OH)D3 into 1,25(OH)2D3. First, 25-hydroxyvitamin D3-1α-hydroxylase mRNA was identified in cultured VSMCs by real-time polymerase chain reaction. Second, in cells treated daily (3 days) with parathyroid hormone (66 nmol/L), estradiol-17β (30 nmol/L), raloxifene (3 μmol/L), and the phytoestrogens genistein (3 μmol/L), biochainin A (3 μmol/L), and 6-carboxy biochainin A (30 nmol/L), 25-hydroxyvitamin D3-1α-hydroxylase mRNA increased by 43 ± 13%, (P<0.05) 7 ± 24% (P=NS), 176±28% (P<0.01), 65 ± 11% (P>0.05), 152 ± 24% (P<0.01), and 71 ± 9% (P<0.05), respectively. Third, production of 1,25(OH)2D 3 from 25(OH)D3 was seen with a Km of 25 ng/mL and increased dose dependently after treatment with parathyroid hormone, genistein, and the phytosetrogen derivative 6-carboxy biochainin A. Estradiol-17β and biochainin A also increased the generation of 1,25(OH)2D3 by 40 ± 23% (P<0.05) and 55 ± 13% (P<0.05), respectively. Conclusions - We provide here the first evidence for the expression of an enzymatically active 25(OH)D3 -1α-hydroxylase system in human VSMCs, which can be upregulated by parathyroid hormone and estrogenic compounds. Because exogenous vitamin D inhibits VSMC proliferation, the role of this system as an autocrine mechanism to curb changes in VSMC proliferation and phenotype is a subject for future investigation.

Original languageEnglish
Pages (from-to)1666-1671
Number of pages6
JournalCirculation
Volume111
Issue number13
DOIs
StatePublished - 5 Apr 2005

Keywords

  • Molecular biology
  • Muscle, smooth
  • Parathyroid hormone
  • Vasculature
  • Vitamin D

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