Micro RNA-550a interferes with vitamin D metabolism in peripheral B cells of patients with diabetes

Cell Biochem Funct. 2016 Dec;34(8):640-646. doi: 10.1002/cbf.3240.

Abstract

The pathogenesis of diabetes is to be further investigated. Vitamin D3 (VitD3) can improve diabetes. Micro RNAs (miR) are involved in regulating cell activities. This study tests a hypothesis that miR-550a interferes with the metabolism of VitD3 in peripheral B cells. In this study, blood samples were collected from patients with diabetes and healthy persons. The B cells were isolated from the blood samples to be treated with tumor necrosis factor (TNF)-α. The B cells were then collected and analyzed for the expression of miR-550a and cyp27b1. The results showed that B cells from healthy subjects were capable of converting VitD metabolite calcidiol to calcitriol, which was impaired in B cells collected from diabetic patients. The diabetic patients showed lower bone mineral density than that in healthy subject. The miR-550a was negatively correlated with bone mineral density and the Levels of cyp27b1 in peripheral B cells of patients with diabetes. In vitro study showed that TNF-α increased miR-550a expression and inhibited the expression of cyp27b1 in B cells. miR-550a mediated the effects of TNF-α on inducing chromatin remodeling at the cyp27b1 gene locus. In conclusion, miR-550a mediates the TNF-α-induced suppression of cyp27b1 expression in peripheral B cells of patients with diabetes, which can be blocked by inhibition of miR-550a.

Keywords: B cells; Cyp27b1; TNF-α; Vitamin D3; micro RNA.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Adult
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism*
  • Bone Density / drug effects
  • Calcifediol / metabolism
  • Calcitriol / metabolism
  • Chromatin Assembly and Disassembly / drug effects
  • Diabetes Mellitus / metabolism*
  • Early Growth Response Protein 1 / metabolism
  • Female
  • Genetic Loci
  • Histone Deacetylase 1 / metabolism
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation / drug effects
  • Vitamin D / metabolism*

Substances

  • EGR1 protein, human
  • Early Growth Response Protein 1
  • MIRN550 microRNA, human
  • MicroRNAs
  • Tumor Necrosis Factor-alpha
  • Vitamin D
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • CYP27B1 protein, human
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Calcitriol
  • Calcifediol