MicroRNA-132 targets HB-EGF upon IgE-mediated activation in murine and human mast cells

Cell Mol Life Sci. 2012 Mar;69(5):793-808. doi: 10.1007/s00018-011-0786-3. Epub 2011 Aug 19.

Abstract

MicroRNAs provide an additional layer in the regulation of gene expression acting as repressors with several targets at the posttranscriptional level. This study describes microRNA expression patterns during differentiation and activation of mast cells. The expression levels of 567 different mouse miRNAs were compared by microarray between c-Kit+ committed progenitors, mucosal mast cells, resting and IgE-crosslinked BMMCs in vitro. The strongest upregulation of miR-132 upon IgE-mediated activation was validated in human cord blood-derived mast cells as well. HB-EGF growth factor also upregulated upon activation and was ranked high by more prediction algorithms. Co-transfection of miR-132 mimicking precursor and the 3'UTR of human Hbegf-containing luciferase vector proves that the predicted binding site is functional. In line with this, neutralization of miR-132 by anti-miR inhibitor leads to sustained production of HB-EGF protein in activated mast cells. Our data provide a novel example for negative regulation of a growth factor by an upregulated miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Binding Sites
  • Cell Differentiation
  • Fetal Blood / cytology
  • Gene Expression Profiling
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Immunoglobulin E / metabolism*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Mast Cells / cytology
  • Mast Cells / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism*
  • Transcriptional Activation
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • HBEGF protein, human
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • MIRN132 microRNA, human
  • MicroRNAs
  • Immunoglobulin E