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Published on: July 19, 2018
Iron increases the profibrotic properties of the senescent peritoneal mesothelial cells
1Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Greater Poland Voivodeship, Poland.
Background:
Treatment of anemia in peritoneal dialysis patients often requires intravenous iron supplementation. Iron diffuses into the peritoneal cavity and is injurious to the peritoneum. We studied how intermittent exposure to iron changes the properties of the senescent peritoneal mesothelial cells (MC).
Methods:
Replicative senescence was induced in MC in control medium (Con) or in control medium with intermittent exposure to iron isomaltoside 15 µg/dL (Con-IIS). After 10 passages properties of MC from both groups were compared to MC not exposed to replicative senescence.
Results:
In senescent MC population doubling time was elongated, intracellular generation of free radicals and staining for β-galactosidase was stronger than in MC not exposed to replicative senescence. All these effects were stronger in MC intermittently exposed to IIS. In these cells intracellular iron content was also higher. Also expression of genes p21 and p53 was stronger in MC intermittently treated with IIS. In senescent cells higher release and expression of IL6 and TGFβ1 was observed and that effect was stronger in MC treated with iron. Senescent MC had reduced fibrinolytic activity, what may predispose to the peritoneal fibrosis. Synthesis of collagen was higher in senescent cells, more in MC treated with iron.
Conclusion:
MC aging results in change of their genotype and phenotype which lead to their profibrotic effect. Exposure to iron enhances these changes.
Insights
Iron supplementation in peritoneal dialysis patients can harm the peritoneum. Intermittent iron exposure exacerbates aging in peritoneal mesothelial cells, increasing fibrosis risk.
Area of Science:
- Cell Biology
- Nephrology
- Toxicology
Background:
- Peritoneal dialysis patients often require intravenous iron for anemia.
- Iron can accumulate in the peritoneal cavity, potentially harming mesothelial cells.
- The effects of iron exposure on senescent peritoneal mesothelial cells are not fully understood.
Purpose of the Study:
- To investigate how intermittent iron exposure affects the properties of senescent peritoneal mesothelial cells (MC).
Main Methods:
- Replicative senescence was induced in MC.
- Cells were exposed to intermittent iron isomaltoside (IIS) or control medium.
- Properties of senescent MC were compared to non-senescent MC.
Main Results:
- Senescent MC exhibited increased doubling time, free radical generation, and β-galactosidase activity.
- Intermittent iron exposure amplified these senescence markers and increased intracellular iron.
- Iron-treated senescent cells showed higher expression of p21, p53, IL6, and TGFβ1, with reduced fibrinolytic activity and increased collagen synthesis.
Conclusions:
- Cellular aging in MC alters their phenotype towards a profibrotic state.
- Iron exposure intensifies these aging-related changes, potentially increasing peritoneal fibrosis risk.
