MicroRNA-200b regulates distal airway development by maintaining epithelial integrity.
Naghmeh KhoshgooRobin VisserLandon FalkChelsea A DayDustin AmeisBarbara M IwasiowFuqin ZhuArzu ÖztürkSujata BasuMolly PindAgnes FresnosaMike JacksonVinaya Kumar SiragamGerald StelmackGeoffrey G HicksAndrew J HalaykoRichard KeijzerPublished in: Scientific reports (2017)
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.
Keyphrases
- cell cycle
- lung function
- pulmonary hypertension
- high fat diet induced
- endothelial cells
- cell proliferation
- gene expression
- cystic fibrosis
- oxidative stress
- chronic obstructive pulmonary disease
- poor prognosis
- minimally invasive
- squamous cell carcinoma
- air pollution
- type diabetes
- metabolic syndrome
- adipose tissue
- endoplasmic reticulum stress
- copy number
- long non coding rna
- small molecule
- wild type
- lymph node metastasis
- data analysis
- squamous cell