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Published on: June 25, 2017
High glucose accelerates the life cycle of the in vivo exposed mesothelium
A Shostak1, V Wajsbrot, L Gotloib
1Department of Nephrology and Hypertension, Ha'Emek Medical Center, Afula, Israel.
Background:
Mouse mesothelium exposed in vivo for 30 days to high glucose solutions develop morphological changes that characterize a population of cells near the end of their life span.
Methods:
The present study was designed to explore, in mesothelial cell imprints, whether these changes could derive from an early acceleration of the cell population life cycle in mice exposed for periods of up to 30 days to a 4.25% glucose fluid (236 mmol/L/L) prepared in Hank's balanced salt solution (HBSS). Three critical points of the cell's life cycle were evaluated: the G1 checkpoint [proliferating cell nuclear antigen (PCNA) expression], DNA synthesis ((3)H-thymidine incorporation), and the prevalence of mitosis.
Results:
Cell populations exposed to a high glucose concentration showed an initial acceleration of their life cycle, as sustained by a peak of mitosis at two hours, an early increase of DNA incorporation sustained during the first 24 hours, as well as a top level of PCNA expression after three to four hours. These significantly higher values, compared with the control animals treated with HBSS, collapsed after 24 hours and were nil after 30 days of exposure.
Conclusions:
Exposure to a high glucose concentration induced an early and short-lived acceleration of the mesothelial cell cycle, and with a longer exposure this was followed by a depletion of the growth capabilities of the exposed monolayer.
Insights
High glucose exposure initially accelerates mesothelial cell cycles, indicated by increased mitosis and DNA synthesis. However, this effect is short-lived, leading to depleted growth capabilities with prolonged exposure.
Area of Science:
- Cell Biology
- Physiology
Background:
- Mouse mesothelium exposed to high glucose develops morphological changes.
- These changes suggest cells are nearing the end of their lifespan.
Purpose of the Study:
- To investigate if high glucose accelerates the mesothelial cell cycle.
- To evaluate changes in cell cycle checkpoints, DNA synthesis, and mitosis.
Main Methods:
- Mesothelial cell imprints from mice exposed to 4.25% glucose or HBSS.
- Assessed proliferating cell nuclear antigen (PCNA) expression.
- Measured (3)H-thymidine incorporation and mitosis prevalence.
Main Results:
- High glucose initially accelerated the cell cycle with peak mitosis at 2 hours.
- Increased DNA synthesis and PCNA expression observed within hours.
- These effects diminished after 24 hours and were absent after 30 days.
Conclusions:
- High glucose causes a transient acceleration of the mesothelial cell cycle.
- Prolonged exposure leads to a depletion of cellular growth capacity.
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