Iron increases the profibrotic properties of the senescent peritoneal mesothelial cells.


Journal

The International journal of artificial organs
ISSN: 1724-6040
Titre abrégé: Int J Artif Organs
Pays: United States
ID NLM: 7802649

Informations de publication

Date de publication:
Sep 2023
Historique:
medline: 7 9 2023
pubmed: 11 8 2023
entrez: 11 8 2023
Statut: ppublish

Résumé

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). 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. 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. MC aging results in change of their genotype and phenotype which lead to their profibrotic effect. Exposure to iron enhances these changes.

Sections du résumé

BACKGROUND UNASSIGNED
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 UNASSIGNED
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 UNASSIGNED
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 UNASSIGNED
MC aging results in change of their genotype and phenotype which lead to their profibrotic effect. Exposure to iron enhances these changes.

Identifiants

pubmed: 37564017
doi: 10.1177/03913988231192123
doi:

Substances chimiques

Iron E1UOL152H7

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

473-480

Auteurs

Andrzej Breborowicz (A)

Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Greater Poland Voivodeship, Poland.
Department of Histology, Collegium Medicum, Zielona Gora University, Zielona Gora, Poland.

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