calcitriol and Pulmonary-Fibrosis

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 D. 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.. 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.. 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.

Topics: A549 Cells; Animals; Bleomycin; Cellular Senescence; DNA Damage; Epithelial Cells; Female; Humans; Lung; Mice, Inbred C57BL; Myofibroblasts; Pulmonary Fibrosis; Vitamin D