| RRC ID |
58151
|
| 著者 |
Li K, Li M, Li W, Yu H, Sun X, Zhang Q, Li Y, Li X, Li Y, Abel ED, Wu Q, Chen H.
|
| タイトル |
Airway epithelial regeneration requires autophagy and glucose metabolism.
|
| ジャーナル |
Cell Death Dis
|
| Abstract |
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.
|
| 巻・号 |
10(12)
|
| ページ |
875
|
| 公開日 |
2019-11-20
|
| DOI |
10.1038/s41419-019-2111-2
|
| PII |
10.1038/s41419-019-2111-2
|
| PMID |
31748541
|
| PMC |
PMC6868131
|
| MeSH |
Animals
Autophagy
Cell Differentiation / physiology
Epithelial Cells / cytology
Epithelial Cells / metabolism
Epithelial Cells / physiology
Glucose / metabolism*
Humans
Lung / cytology
Lung / metabolism
Lung / physiology*
Mice
Mice, Inbred C57BL
Regeneration / physiology*
Stem Cells / cytology
Stem Cells / metabolism
Stem Cells / physiology*
|
| IF |
6.304
|
| 引用数 |
1
|
| リソース情報 |
| 実験動物マウス |
RBRC02975 |
