Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/7644
Detrimental pro-senescence effects of vitamin D on lung fibrosis
Mol Med. 2018 Dec 19;24(1):64.
BACKGROUND: The multiple biological effects of vitamin D and its novel activities on inflammation and redox homeostasis have raised high expectations on its use as a therapeutic agent for multiple fibrogenic conditions. We have assessed the therapeutic effects of 1α,25-Dihydroxyvitamin D3, the biologically active form of vitamin D, in the context of lung fibrosis. METHODS: We have used representative cellular models for alveolar type II cells and human myofibroblasts. The extension of DNA damage and cellular senescence have been assessed by immunofluorescence, western-blot and senescence-associated β-galactosidase activity. We have also set up a murine model for lung fibrosis by intraperitoneal injections of bleomycin. RESULTS: Vitamin D induces cellular senescence in bleomycin-treated alveolar epithelial type II cells and aggravates the lung pathology induced by bleomycin. These effects are probably due to an alteration of the cellular DNA double-strand breaks repair in bleomycin-treated cells. CONCLUSIONS: The detrimental effects of vitamin D in the presence of a DNA damaging agent might preclude its use as an antifibrogenic agent for pulmonary fibrosis characterized by DNA damage occurrence and cellular senescence.
A549 Cells | Animals | Bleomycin | Cellular Senescence | Epithelial Cells | Female | Humans | Lung | Mice, Inbred C57BL | Myofibroblasts | Pulmonary Fibrosis | Vitamin D | DNA Damage
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