Effects of Hypocalcemic Vitamin D Analogs in the Expression of DNA Damage Induced in Minilungs from hESCs: Implications for Lung Fibrosis
| Autor: | Alberto Zambrano, Esmeralda Magro-Lopez, Irene Chamorro-Herrero |
|---|---|
| Přispěvatelé: | Instituto de Salud Carlos III |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Vitamin D analogs
DNA damage Pulmonary Fibrosis Human Embryonic Stem Cells Catalysis Inorganic Chemistry Bleomycin Mice Minilungs Vitamin D and neurology Animals Humans Human pluripotent stem cells Physical and Theoretical Chemistry Vitamin D Calcipotriol Molecular Biology Spectroscopy Chemistry Organic Chemistry Lung fibrosis General Medicine Paricalcitol respiratory system human pluripotent stem cells hESCs minilungs vitamin D vitamin D analogs paricalcitol calcipotriol lung fibrosis Computer Science Applications Cancer research DNA Damage |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 9; Pages: 4921 |
| Popis: | BackgroundIn our previous work, we evaluated the therapeutic effects of 1α,25-Dihydroxyvitamin D3, the biologically active form of vitamin D, in the context of bleomycin-induced lung fibrosis. Contrary to the expected, vitamin D supplementation increased DNA damage expression and cellular senescence in alveolar epithelial type II cells and aggravated the overall lung pathology induced in mice by bleomycin. These effects were probably due to an alteration of the cellular DNA double-strand breaks repair capability. In the present work we have evaluated the effects of two hypocalcemic vitamin D analogs (calcipotriol and paricalcitol) in the expression of DNA damage in the context of minilungs derived from human embryonic stem cells and in the cell line A549.ResultsAs in the case of the cell line A549, bleomycin can induce DNA damage in the generated minilungs enriched in alveolar cells. The results indicate that, in contrast to vitamin D, the treatment of the minilungs with the hypocalcemic analogs reduce significantly the bulk of DNA damage expression in both bidimensional arrays of epithelial cells (2D minilungs) and lung bud organoids (3D minilungs). The initial evaluation of a battery of commercially available vitamin D analogs shows a significant reduction in A549 cells of gH2AFX expression levels, a marker of DNA damage, cell senescence and aging.ConclusionsThe treatments based in hypocalcemic vitamin D analogs might be used to reduce the bulk of DNA damage and eventually the subsequent cell senescence expression that underlie lung conditions as those that can evolve with fibrosis. |
| Databáze: | OpenAIRE |
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