Vitamin D/VDR signaling suppresses microRNA-802-induced apoptosis of keratinocytes in oral lichen planus

FASEB J. 2019 Jan;33(1):1042-1050. doi: 10.1096/fj.201801020RRR. Epub 2018 Aug 3.

Abstract

Vitamin D is known to play a protective role in inflammatory diseases. Although the suppressive effect of vitamin D/vitamin D receptor (VDR) signaling has been shown in the context of oral lichen planus (OLP), the molecular basis of its regulatory function remains poorly understood. Herein, we reported that miR-802 overexpression in OLP could aggravate apoptosis of oral keratinocytes by targeting B-cell lymphoma 2 mRNA. In addition, vitamin D/VDR signaling was able to suppress miR-802 expression in LPS-treated or activated CD4+ T cell-stimulated human oral keratinocytes by blocking NF-κB pathways, thereby inhibiting OLP apoptosis. Consistent with the results in vitro, we showed that miR-802 expression was enhanced in oral keratinocytes from VDR-/- mice, and an inverse correlation between VDR and miR-802 was found in human biopsy specimens of OLP. Collectively, our data suggest that vitamin D/VDR signaling suppresses oral keratinocyte apoptosis by targeting miR-802.-Zhao, B., Xu, N., Li, R., Yu, F., Zhang, F., Yang, F., Ge, X., Li, Y. C., Du, J. Vitamin D/VDR signaling suppresses microRNA-802-induced apoptosis of keratinocytes in oral lichen planus.

Keywords: Bcl2; NF-κB; vitamin D receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Apoptosis / physiology*
  • Cell Line
  • Female
  • Humans
  • Keratinocytes / cytology*
  • Lichen Planus, Oral / genetics
  • Lichen Planus, Oral / metabolism
  • Lichen Planus, Oral / pathology*
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / physiology*
  • Middle Aged
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism*
  • Signal Transduction*
  • Up-Regulation
  • Vitamin D / metabolism*

Substances

  • MIRN802 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Calcitriol
  • Vitamin D