| RRC ID |
58401
|
| 著者 |
Li X, Wu J, Sun X, Wu Q, Li Y, Li K, Zhang Q, Li Y, Abel ED, Chen H.
|
| タイトル |
Autophagy Reprograms Alveolar Progenitor Cell Metabolism in Response to Lung Injury.
|
| ジャーナル |
Stem Cell Reports
|
| Abstract |
Autophagy is a protective cellular mechanism in response to stress conditions. However, whether autophagy is required for maintenance of the alveolar epithelium is unknown. Here, we report that the loss of autophagy-related 5 (Atg5) in AT2 cells worsened bleomycin-induced lung injury. Mechanistically, during bleomycin injury, autophagy downregulated lipid metabolism but upregulated glucose metabolism in AT2 cells for alveolar repair. Chemical blockade of fatty acid synthesis promoted organoid growth of AT2 cells and counteracted the effects of autophagy loss on bleomycin injury. However, genetic loss of glucose transporter 1, interference with glycolysis, or interference with the pentose phosphate pathway reduced the proliferation of AT2 cells. Inhibition of glucose metabolism exacerbated the effects of bleomycin injury. Failure of autophagy generated additional hydrogen peroxide, which reduced AT2 cell proliferation. These data highlight an essential role for autophagy in reprogramming the metabolism of alveolar progenitor cells to meet energy needs for alveolar epithelial regeneration.
|
| 巻・号 |
14(3)
|
| ページ |
420-432
|
| 公開日 |
2020-3-10
|
| DOI |
10.1016/j.stemcr.2020.01.008
|
| PII |
S2213-6711(20)30029-1
|
| PMID |
32059792
|
| PMC |
PMC7066233
|
| MeSH |
Alveolar Epithelial Cells / metabolism*
Alveolar Epithelial Cells / pathology*
Animals
Autophagy*
Bleomycin
Cell Proliferation
Cellular Reprogramming*
Fatty Acids / biosynthesis
Glucose Transporter Type 1 / metabolism
Glycolysis
Hydrogen Peroxide / metabolism
Lung Injury / metabolism*
Lung Injury / pathology*
Mice, Inbred C57BL
Oxidative Stress
Pentose Phosphate Pathway
Stem Cells / metabolism*
|
| IF |
6.032
|
| 引用数 |
0
|
| リソース情報 |
| 実験動物マウス |
RBRC02975 |
