MicroRNA-200b regulates distal airway development by maintaining epithelial integrity

Autor: Naghmeh Khoshgoo, Robin Visser, Landon Falk, Chelsea A. Day, Dustin Ameis, Barbara M. Iwasiow, Fuqin Zhu, Arzu Öztürk, Sujata Basu, Molly Pind, Agnes Fresnosa, Mike Jackson, Vinaya Kumar Siragam, Gerald Stelmack, Geoffrey G. Hicks, Andrew J. Halayko, Richard Keijzer
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-017-05412-y
Popis: Abstract miR-200b plays a role in epithelial-to-mesenchymal transition (EMT) in cancer. We recently reported abnormal expression of miR-200b in the context of human pulmonary hypoplasia in congenital diaphragmatic hernia (CDH). Smaller lung size, a lower number of airway generations, and a thicker mesenchyme characterize pulmonary hypoplasia in CDH. The aim of this study was to define the role of miR-200b during lung development. Here we show that miR-200b−/− mice have abnormal lung function due to dysfunctional surfactant, increased fibroblast-like cells and thicker mesenchyme in between the alveolar walls. We profiled the lung transcriptome in miR-200b−/− mice, and, using Gene Ontology analysis, we determined that the most affected biological processes include cell cycle, apoptosis and protein transport. Our results demonstrate that miR-200b regulates distal airway development through maintaining an epithelial cell phenotype. The lung abnormalities observed in miR-200b−/− mice recapitulate lung hypoplasia in CDH.
Databáze: Directory of Open Access Journals
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