Abstract
Background: The gene expression profile of bronchial epithelial regeneration in health and disease is not well understood.
Aims: To understand the gene expression profile of differentiating normal human bronchial epithelial (NHBE) cells.
Methods: At 7 time points over a 28 day culture period morphological and global gene expression analyses were performed.
Results: Fully differentiated NHBEs exhibited goblet and ciliated cells along with significant increases in epithelial resistance (P<0.001), MUC5AC mRNA (P<0.001) and mucin production (P<0.001). 1720 transcripts were significantly differentially expressed during differentiation (fold change >1.4; adjusted P value <0.001). MFUZZ cluster analysis (exC) identified 5 early stage (Days 0-7) and 4 late stage clusters (Days 7-28). Gene ontology exC analysis identified a decrease in cell cycle (early exC1, P=1.8x10-12) and an increase in cilium organization and morphogenesis (early exC2, P=7.5x10-9; early exC3, P=2.5x10-5; late exC2, P=2.5x10-29). Adhesion molecule, chemokine/cytokine, matrix metallopeptidase, antimicrobial and inflammatory genes decreased (late exC4) and mucin genes increased (early exC4). Transcription factor (TF) analysis detected significant increases in FOXJ1, RFX2 & RFX3 expression.
Conclusions: This data is a comprehensive list of genes important in bronchial mucociliary differentiation. An undifferentiated epithelium is primed for inflammation and ceases proliferation during differentiation under the influence of ciliogenic TFs. This provides a reference for studying disordered epithelial regeneration in asthma.
- Copyright ©the authors 2016