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

Excessive secretion of airway mucus and fluid accumulation are the common features of many respiratory diseases, which, in turn, induce cell hypoxia in the airway epithelium, resulting in epithelial–mesenchymal transition (EMT) and ultimately fibrosis. However, the mechanisms of EMT induced by hypox...

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Autores principales: Hou, Yapeng, Ding, Yan, Du, Danni, Yu, Tong, Zhou, Wei, Cui, Yong, Nie, Hongguang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696177/
https://www.ncbi.nlm.nih.gov/pubmed/34955855
http://dx.doi.org/10.3389/fphar.2021.783946
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author Hou, Yapeng
Ding, Yan
Du, Danni
Yu, Tong
Zhou, Wei
Cui, Yong
Nie, Hongguang
author_facet Hou, Yapeng
Ding, Yan
Du, Danni
Yu, Tong
Zhou, Wei
Cui, Yong
Nie, Hongguang
author_sort Hou, Yapeng
collection PubMed
description Excessive secretion of airway mucus and fluid accumulation are the common features of many respiratory diseases, which, in turn, induce cell hypoxia in the airway epithelium, resulting in epithelial–mesenchymal transition (EMT) and ultimately fibrosis. However, the mechanisms of EMT induced by hypoxia in the airway are currently unclear. To mimic the status of edematous fluid retention in the airway, we cultured primary mouse tracheal epithelial cells (MTECs) in a liquid–liquid interface (LLI) mode after full differentiation in a classic 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 other airway epithelial cells were found to be enriched in the ribosome by our analysis of an MTEC single-cell RNA sequencing data set 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 results showed that ribosome biogenesis was significantly upregulated in basal cells, whereas the inhibition of ribosome biogenesis alleviated the phosphorylation of the mammalian target of rapamycin/AKT and abrogated hypoxia-induced EMT in MTECs. Collectively, these observations strongly suggest that basal cells in the airway epithelium may mediate the process of hypoxia-induced EMT, partly through enhancing ribosome biogenesis.
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spelling pubmed-86961772021-12-24 Airway Basal Cells Mediate Hypoxia-Induced EMT by Increasing Ribosome Biogenesis Hou, Yapeng Ding, Yan Du, Danni Yu, Tong Zhou, Wei Cui, Yong Nie, Hongguang Front Pharmacol Pharmacology Excessive secretion of airway mucus and fluid accumulation are the common features of many respiratory diseases, which, in turn, induce cell hypoxia in the airway epithelium, resulting in epithelial–mesenchymal transition (EMT) and ultimately fibrosis. However, the mechanisms of EMT induced by hypoxia in the airway are currently unclear. To mimic the status of edematous fluid retention in the airway, we cultured primary mouse tracheal epithelial cells (MTECs) in a liquid–liquid interface (LLI) mode after full differentiation in a classic 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 other airway epithelial cells were found to be enriched in the ribosome by our analysis of an MTEC single-cell RNA sequencing data set 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 results showed that ribosome biogenesis was significantly upregulated in basal cells, whereas the inhibition of ribosome biogenesis alleviated the phosphorylation of the mammalian target of rapamycin/AKT and abrogated hypoxia-induced EMT in MTECs. Collectively, these observations strongly suggest that basal cells in the airway epithelium may mediate the process of hypoxia-induced EMT, partly through enhancing ribosome biogenesis. Frontiers Media S.A. 2021-12-09 /pmc/articles/PMC8696177/ /pubmed/34955855 http://dx.doi.org/10.3389/fphar.2021.783946 Text en Copyright © 2021 Hou, Ding, Du, Yu, Zhou, Cui and Nie. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Hou, Yapeng
Ding, Yan
Du, Danni
Yu, Tong
Zhou, Wei
Cui, Yong
Nie, Hongguang
Airway Basal Cells Mediate Hypoxia-Induced EMT by Increasing Ribosome Biogenesis
title Airway Basal Cells Mediate Hypoxia-Induced EMT by Increasing Ribosome Biogenesis
title_full Airway Basal Cells Mediate Hypoxia-Induced EMT by Increasing Ribosome Biogenesis
title_fullStr Airway Basal Cells Mediate Hypoxia-Induced EMT by Increasing Ribosome Biogenesis
title_full_unstemmed Airway Basal Cells Mediate Hypoxia-Induced EMT by Increasing Ribosome Biogenesis
title_short Airway Basal Cells Mediate Hypoxia-Induced EMT by Increasing Ribosome Biogenesis
title_sort airway basal cells mediate hypoxia-induced emt by increasing ribosome biogenesis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8696177/
https://www.ncbi.nlm.nih.gov/pubmed/34955855
http://dx.doi.org/10.3389/fphar.2021.783946
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