Airway epithelial regeneration requires autophagy and glucose metabolism

Efficient repair of injured epithelium by airway progenitor cells could prevent acute inflammation from progressing into chronic phase in lung. Here, we used small molecules, genetic loss-of-function, organoid cultures, and in vivo lung-injury models to show that autophagy is essential for maintaini...

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Bibliographic Details
Published in:Cell death & disease 2019-11, Vol.10 (12), p.875-14, Article 875
Main Authors: Li, Kuan, Li, Minmin, Li, Wenli, Yu, Hongzhi, Sun, Xin, Zhang, Qiuyang, Li, Yu, Li, Xue, Li, Yue, Abel, E. Dale, Wu, Qi, Chen, Huaiyong
Format: Article
Language:English
Subjects:
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Animals
Antibodies
Autophagy
Biochemistry
Biomedical and Life Sciences
Cell Biology
Cell Culture
Cell differentiation
Cell Differentiation - physiology
Cell proliferation
Epithelial Cells - cytology
Epithelial Cells - metabolism
Epithelial Cells - physiology
Epithelium
Glucose
Glucose - metabolism
Glucose transporter
Glycolysis
Humans
Hypersensitivity
Immunology
Inflammation
Life Sciences
Lung - cytology
Lung - metabolism
Lung - physiology
Lungs
Metabolism
Mice
Mice, Inbred C57BL
Organoids
Ovalbumin
Phagocytosis
Progenitor cells
Regeneration - physiology
Respiratory tract
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
Stem Cells - physiology
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Summary:Efficient repair of injured epithelium by airway progenitor cells could prevent acute inflammation from progressing into chronic phase in lung. Here, we used small molecules, genetic loss-of-function, organoid cultures, and in vivo lung-injury models to show that autophagy is essential for maintaining the pool of airway stem-like vClub cells by promoting their proliferation during ovalbumin-induced acute inflammation. Mechanistically, impaired autophagy disrupted glucose uptake in vClub progenitor cells, and either reduced accessibility to glucose or partial inhibition of glycolysis promoted the proliferative capacity of vClub progenitor cells and their daughter Club cells. However, glucose deprivation or glycolysis blockade abrogated the proliferative capacity of airway vClub cells and Club cells but promoted ciliated and goblet cell differentiation. Deficiency of glucose transporter-1 suppressed the proliferative capacity of airway progenitor cells after ovalbumin challenge. These findings suggested that autophagy and glucose metabolism are essential for the maintenance of airway epithelium at steady state and during allergic inflammation.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-019-2111-2