Secretory galectin-3 induced by glucocorticoid stress triggers stemness exhaustion of hepatic progenitor cells
© 2020 Yang et al..
Adult progenitor cell populations typically exist in a quiescent state within a controlled niche environment. However, various stresses or forms of damage can disrupt this state, which often leads to dysfunction and aging. We built a glucocorticoid (GC)-induced liver damage model of mice, found that GC stress induced liver damage, leading to consequences for progenitor cells expansion. However, the mechanisms by which niche factors cause progenitor cells proliferation are largely unknown. We demonstrate that, within the liver progenitor cells niche, Galectin-3 (Gal-3) is responsible for driving a subset of progenitor cells to break quiescence. We show that GC stress causes aging of the niche, which induces the up-regulation of Gal-3. The increased Gal-3 population increasingly interacts with the progenitor cell marker CD133, which triggers focal adhesion kinase (FAK)/AMP-activated kinase (AMPK) signaling. This results in the loss of quiescence and leads to the eventual stemness exhaustion of progenitor cells. Conversely, blocking Gal-3 with the inhibitor TD139 prevents the loss of stemness and improves liver function. These experiments identify a stress-dependent change in progenitor cell niche that directly influence liver progenitor cell quiescence and function.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:295 |
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| Enthalten in: |
The Journal of biological chemistry - 295(2020), 49 vom: 04. Dez., Seite 16852-16862 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, Fan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.05.2021 Date Revised 29.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1074/jbc.RA120.012974 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM31559733X |
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| 245 | 1 | 0 | |a Secretory galectin-3 induced by glucocorticoid stress triggers stemness exhaustion of hepatic progenitor cells |
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| 500 | |a Date Completed 04.05.2021 | ||
| 500 | |a Date Revised 29.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 Yang et al. | ||
| 520 | |a Adult progenitor cell populations typically exist in a quiescent state within a controlled niche environment. However, various stresses or forms of damage can disrupt this state, which often leads to dysfunction and aging. We built a glucocorticoid (GC)-induced liver damage model of mice, found that GC stress induced liver damage, leading to consequences for progenitor cells expansion. However, the mechanisms by which niche factors cause progenitor cells proliferation are largely unknown. We demonstrate that, within the liver progenitor cells niche, Galectin-3 (Gal-3) is responsible for driving a subset of progenitor cells to break quiescence. We show that GC stress causes aging of the niche, which induces the up-regulation of Gal-3. The increased Gal-3 population increasingly interacts with the progenitor cell marker CD133, which triggers focal adhesion kinase (FAK)/AMP-activated kinase (AMPK) signaling. This results in the loss of quiescence and leads to the eventual stemness exhaustion of progenitor cells. Conversely, blocking Gal-3 with the inhibitor TD139 prevents the loss of stemness and improves liver function. These experiments identify a stress-dependent change in progenitor cell niche that directly influence liver progenitor cell quiescence and function | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a AMP-activated kinase (AMPK) | |
| 650 | 4 | |a Cell senescence | |
| 650 | 4 | |a cell cycle | |
| 650 | 4 | |a cellular senescence | |
| 650 | 4 | |a galectin | |
| 650 | 4 | |a galectin-3 | |
| 650 | 4 | |a glycoprotein | |
| 650 | 4 | |a liver injury | |
| 650 | 4 | |a proliferation | |
| 650 | 4 | |a protein interaction | |
| 650 | 4 | |a protein-protein interaction | |
| 650 | 4 | |a quiescence | |
| 650 | 4 | |a stem cells | |
| 650 | 4 | |a stemness exhaustion | |
| 650 | 7 | |a AC133 Antigen |2 NLM | |
| 650 | 7 | |a Cephalosporins |2 NLM | |
| 650 | 7 | |a Cyclin-Dependent Kinase Inhibitor p16 |2 NLM | |
| 650 | 7 | |a Galectin 3 |2 NLM | |
| 650 | 7 | |a Glycopeptides |2 NLM | |
| 650 | 7 | |a RNA, Small Interfering |2 NLM | |
| 650 | 7 | |a TD 1792 |2 NLM | |
| 650 | 7 | |a Dexamethasone |2 NLM | |
| 650 | 7 | |a 7S5I7G3JQL |2 NLM | |
| 650 | 7 | |a Focal Adhesion Kinase 1 |2 NLM | |
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| 650 | 7 | |a Ptk2 protein, mouse |2 NLM | |
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| 700 | 1 | |a Zhang, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Xueying |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Xue, Mengjuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Huiyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Xiaona |e verfasserin |4 aut | |
| 700 | 1 | |a Bao, Zhijun |e verfasserin |4 aut | |
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