AUTHOR=Hou Yapeng , Ding Yan , Du Danni , Yu Tong , Zhou Wei , Cui Yong , Nie Hongguang 

TITLE=Airway Basal Cells Mediate Hypoxia-Induced EMT by Increasing Ribosome Biogenesis

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.783946

DOI=10.3389/fphar.2021.783946

ISSN=1663-9812

ABSTRACT=Excessive secretion of airway mucus and fluid accumulation are the common features of many respiratory diseases, which in turn make the cell hypoxia in airway epithelium, result in epithelial-mesenchymal transition (EMT) and ultimately fibrosis. However, the mechanisms of EMT induced by hypoxia in airway are currently unclear. To mimic the status of edematous fluid retention in airway, we cultured primary mouse tracheal epithelial cells (MTECs) in a liquid-liquid interface (LLI) mode, after full differentiation in a classical air-liquid interface (ALI) culture system. The cell hypoxia was verified by the physical characteristics and lactate production in cultured medium, as well as HIF expression in MTECs cultured by LLI mode. EMT was evidenced and mainly mediated by basal cells, supported by flow cytometry and immunofluorescence assay. The differently expressed genes of basal and the other airway epithelial cells were found to be enriched in ribosome by our analysis of MTEC single-cell RNA sequencing dataset, and Myc, the global regulator of ribosome biogenesis was identified to be highly expressed in basal cells. We next separated basal cells from bulk MTECs by flow cytometry, and the real-time PCR result showed that ribosome biogenesis was significantly upregulated in basal cells, whereas the inhibition of ribosome biogenesis alleviated the phosphorylation of mammalian target of rapamycin/ AKT and abrogated hypoxia induced EMT in MTECs. Collectively, these observations strongly suggest that basal cells in airway epithelium may mediate the process of hypoxia induced EMT, partly through enhancing ribosome biogenesis.