4.7 Article

Effects of Hypocalcemic Vitamin D Analogs in the Expression of DNA Damage Induced in Minilungs from hESCs: Implications for Lung Fibrosis

Journal

Publisher

MDPI
DOI: 10.3390/ijms23094921

Keywords

human pluripotent stem cells; hESCs; minilungs; vitamin D; vitamin D analogs; paricalcitol; calcipotriol; lung fibrosis

Funding

  1. Institute of Health Carlos III (ISCIII) [PI19CIII/00003]

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Contrary to expectations, the biologically active form of vitamin D did not have therapeutic effects in bleomycin-induced lung fibrosis but instead aggravated lung pathology. The current study focused on evaluating the effects of two hypocalcemic vitamin D analogs on DNA damage expression.
In our previous work, we evaluated the therapeutic effects of 1 alpha,25-Dihydroxyvitamin D-3, the biologically active form of vitamin D, in the context of bleomycin-induced lung fibrosis. Contrary to the expected, vitamin D supplementation increased the 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 in 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.

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