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Plate IV.429 · Publications

Pulmonary microRNA profiles identify involvement of Creb1 and Sec14l3 in bronchial epithelial changes in allergic asthma

Article in Scientific Reports, 6 April 2017.

Open accessmiRNA, Target, Cancer

  1. Sabine Bartel
  2. Nikola Schulz
  3. Francesca Alessandrini
  4. Andrea C. Schamberger
  5. Philipp Pagel
  6. Fabian J. Theis
  7. Katrin Milger
  8. Elfriede Noessner
  9. Stephen M. Stick
  10. Anthony Kicic
  11. Oliver Eickelberg
  12. Robert J. Freishtat
  13. Susanne Krauss-Etschmann

Abstract

Asthma is highly prevalent, but current therapies cannot influence the chronic course of the disease. It is thus important to understand underlying early molecular events. In this study, we aimed to use microRNAs (miRNAs) - which are critical regulators of signaling cascades - to identify so far uncharacterized asthma pathogenesis pathways. Therefore, deregulation of miRNAs was assessed in whole lungs from mice with ovalbumin (OVA)-induced allergic airway inflammation (AAI). In silico predicted target genes were confirmed in reporter assays and in house-dust-mite (HDM) induced AAI and primary human bronchial epithelial cells (NHBE) cultured at the air-liquid interface. We identified and validated the transcription factor cAMP-responsive element binding protein (Creb1) and its transcriptional co-activators (Crtc1-3) as targets of miR-17, miR-144, and miR-21. Sec14-like 3 (Sec14l3) - a putative target of Creb1 - was down-regulated in both asthma models and in NHBE cells upon IL13 treatment, while it's expression correlated with ciliated cell development and decreased along with increasing goblet cell metaplasia. Finally, we propose that Creb1/Crtc1-3 and Sec14l3 could be important for early responses of the bronchial epithelium to Th2-stimuli. This study shows that miRNA profiles can be used to identify novel targets that would be overlooked in mRNA based strategies.

Cite

@article{bartel2017pulmonary,
  title = {{Pulmonary microRNA profiles identify involvement of Creb1 and Sec14l3 in bronchial epithelial changes in allergic asthma}},
  author = {Bartel, Sabine and Schulz, Nikola and Alessandrini, Francesca and Schamberger, Andrea C. and Pagel, Philipp and Theis, Fabian J. and Milger, Katrin and Noessner, Elfriede and Stick, Stephen M. and Kicic, Anthony and Eickelberg, Oliver and Freishtat, Robert J. and Krauss-Etschmann, Susanne},
  journal = {Scientific Reports},
  publisher = {Springer Science and Business Media LLC},
  year = {2017},
  month = apr,
  doi = {10.1038/srep46026},
  url = {https://doi.org/10.1038/srep46026},
  pmid = {28383034},
  pmcid = {PMC5382551}
}
.bib file