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Secretory galectin-3 induced by glucocorticoid stress triggers stemness exhaustion of hepatic progenitor cells
- Source :
- The Journal of Biological Chemistry
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- 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.
- Subjects :
- Male
glycoprotein
0301 basic medicine
Galectin 3
AMP-Activated Protein Kinases
Biochemistry
Dexamethasone
protein-protein interaction
Mice
cellular senescence
AC133 Antigen
RNA, Small Interfering
Stem Cell Niche
education.field_of_study
galectin
Kinase
Glycopeptides
Cell cycle
Up-Regulation
Cell biology
Liver
RNA Interference
Cell senescence
cell cycle
Stem cell
Signal Transduction
liver injury
AMP-activated kinase (AMPK)
proliferation
Population
Biology
Focal adhesion
03 medical and health sciences
stem cells
galectin-3
stemness exhaustion
Animals
quiescence
protein interaction
Progenitor cell
education
Molecular Biology
Cyclin-Dependent Kinase Inhibitor p16
Cell Proliferation
Galectin
030102 biochemistry & molecular biology
Cell Biology
Cephalosporins
Mice, Inbred C57BL
030104 developmental biology
Focal Adhesion Kinase 1
Liver function
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 295
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....4c026faa9ce2e19d3ec8c3af2714c70e