The MTOR signaling pathway regulates macrophage differentiation from mouse myeloid progenitors by inhibiting autophagy
| Autor: | Furao Liu, Dong Li, Ci Xu, Jiaxi Zhou, Yuan Yao, Fei Wang, Pingting Zhou, Yong Fang, Yanyan Li, Meichao Zhang, Lei Bian, Yuanhua Liu, Qian Wang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Myeloid Research Paper - Basic Science Autophagy-Related Proteins Cell Line 03 medical and health sciences Mice Sequestosome 1 Sequestosome-1 Protein medicine Autophagy Animals Autophagy-Related Protein-1 Homolog Progenitor cell Phosphorylation education Molecular Biology Mechanistic target of rapamycin PI3K/AKT/mTOR pathway Myeloid Progenitor Cells Sirolimus education.field_of_study CD11b Antigen 030102 biochemistry & molecular biology biology Macrophages TOR Serine-Threonine Kinases Granulocyte-Macrophage Colony-Stimulating Factor Cell Differentiation Cell Biology Cell biology Mice Inbred C57BL Haematopoiesis 030104 developmental biology medicine.anatomical_structure Integrin alpha M biology.protein Signal Transduction |
| Zdroj: | Autophagy. 15(7) |
| ISSN: | 1554-8635 |
| Popis: | Understanding of the mechanism for myeloid differentiation provides important insights into the hematopoietic developmental processes. By using an ESC-derived myeloid progenitor cell model, we found that CSF2/GM-CSF triggered macrophage differentiation and activation of the MTOR signaling pathway. Activation or inhibition of the MTOR signaling enhanced or attenuated macrophage differentiation, respectively, suggesting a critical function. We further showed that macroautophagy/autophagy was inhibited with the addition of CSF2. Furthermore, pharmacological inhibition and genetic modification of autophagy enhanced macrophage differentiation and rescued the inhibitory effect on differentiation caused by MTOR inhibition. Thus, the MTOR signaling pathway regulates macrophage differentiation of myeloid progenitors by inhibiting autophagy. Our results provide new insights into the mechanisms for myeloid differentiation and may prove useful for therapeutic applications of hematopoietic and myeloid progenitor cells. Abbreviations: 2-DG: 2-deoxy-D-glucose; ADGRE1/F4/80: adhesion G protein-coupled receptor E1; BM: bone marrow; CQ: chloroquine; ECAR: extracellular acidification rate; ESC: embryonic stem cell; CSF2/GM-CSF: colony stimulating factor 2; CSF3/G-CSF: colony stimulating factor 3; HPC: hematopoietic progenitor cell; ITGAM/CD11b: integrin alpha M; LPS: lipopolysaccharide; MFI: median fluorescence intensity; MTOR: mechanistic target of rapamycin kinase; RPS6KB1/p70S6K1: ribosomal protein S6 kinase, polypeptide 1; shRNA: short hairpin RNA; SQSTM1/p62: sequestosome 1. |
| Databáze: | OpenAIRE |
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