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Detrimental pro-senescence effects of vitamin D on lung fibrosis

Authors :
Trinidad Guijarro
Esmeralda Magro-Lopez
Joana Manso
Ricardo Garcia-Martinez
Maria Jesus Fernandez-Aceñero
Isabel Liste
Alberto Zambrano
Source :
Molecular Medicine, Vol 24, Iss 1, Pp 1-16 (2018)
Publication Year :
2018
Publisher :
BMC, 2018.

Abstract

Abstract 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.

Details

Language :
English
ISSN :
10761551 and 15283658
Volume :
24
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Molecular Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.b5d2860a4b2a4a67945e5895f216f190
Document Type :
article
Full Text :
https://doi.org/10.1186/s10020-018-0064-z