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

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.

MicroRNA-132 enhances transition from inflammation to proliferation during wound healing

“…The TargetScan algorithm identified 2 conserved binding sites for miR-132 in the 3′-UTR of HB-EGF ( Figure 6A). Moreover, HB-EGF has been previously demonstrated as a direct target of miR-132 in human mast cells (26). Therefore, we set out to examine whether HB-EGF is also targeted by miR-132 in human keratinocytes.…”

Human Mast Cell Sensitization with IgE Increases miRNA-210 Expression

“…MicroRNAs (miRNAs) represent a hitherto little-explored layer of control of MCs but have been found in the MC line HMC-1 and in exosomes released from these cells [1]. The increase in the miR-132/212 cluster during MC activation has been reported [2, 3]. We cultured, sensitized, and activated MCs from blood of asthmatic patients and controls [4], and measured histamine release, PGD2 synthesis, and miRNA profiles at each of these stages to explore the spectrum of expressed miRNAs and their relationship to the mediators relevant for distinct stages of allergic response.…”

Mast cell plasticity and sphingosine-1-phosphate in immunity, inflammation and cancer

“…Interestingly, miRNA-146a expression is also increased in splenic CD4+ T lymphocytes in ovalbumin (OVA)-induced mouse asthma models [123] but dampens NF-kB-mediated inflammatory responses [124]. Upregulated miRNA-132 was also reported in activated mouse and human MC [125], whereas miRNA-126 is down-regulated during MC differentiation to positively regulate MC proliferation [126]. MiRNA-126 silencing abolished house dust mite-induced airway hyperresponsiveness, dampened Th2 cytokines and reduced allergic inflammation in a mouse model [127].…”