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MiR-142-3p is associated with aberrant WNT signaling during airway remodeling in asthma

Bartel, S., Carraro, G., Alessandrini, F., Krauss-Etschmann, S., Ricciardolo, F. L. M. & Bellusci, S., Aug-2018, In : American Journal of Physiology - Lung Cellular and Molecular Physiology. 315, 2, p. L328-L333 6 p.

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  • miR-142-3p is associated with aberrant WNT signaling during airway remodeling in asthma

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DOI

  • Sabine Bartel
  • Gianni Carraro
  • Francesca Alessandrini
  • Susanne Krauss-Etschmann
  • Fabio Luigi Massimo Ricciardolo
  • Saverio Bellusci

Asthma is characterized by —Asthma a chronic inflammation and remodeling of the airways. Although inflammation can be controlled, therapeutic options to revert remodeling do not exist. Thus, there is a large and unmet need to understand the underlying molecular mechanisms to develop novel therapies. We previously identified a pivotal role for miR-142-3p in regulating airway smooth muscle (ASM) precursor cell proliferation during lung development by fine-tuning the Wingless/Integrase I (WNT) signaling. Thus, we here aimed to investigate the relevance of this interaction in asthma. We performed quantitative RT-PCR and immune staining in a murine model for ovalbumin-induced allergic airway inflammation and in bronchial biopsies from patients with asthma and isolated primary fibroblasts thereof. miR-142-3p was increased in hyperproliferative regions of lung in murine and human asthma, whereas this microRNA (miRNA) was excluded from regions with differentiated ASM cells. Increases in miR-142-3p were associated with a decrease of its known target Adenomatous polyposis coli. Furthermore, we observed a differential expression of miR-142-3p in bronchial biopsies from patients with early or late onset severe asthma, which coincided with a differential WNT signature. Our data suggest that miR-142-3p is involved in regulating the balance between proliferation and differentiation of ASM cells in asthma, possibly via controlling WNT signaling. Thus, this miRNA might be an interesting target to prevent ASM hyperproliferation in asthma.

Original languageEnglish
Pages (from-to)L328-L333
Number of pages6
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume315
Issue number2
Publication statusPublished - Aug-2018
Externally publishedYes

    Keywords

  • Airway remodeling, Asthma, MiR-142-3p, WNT, LUNG DEVELOPMENT, ALLERGIC-ASTHMA, MICRORNAS, DISEASES, SUSCEPTIBILITY, EXPRESSION, PHENOTYPES, CELLS

ID: 97442619