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Detrimental pro-senescence effects of vitamin D on lung fibrosis
- 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.
- Subjects :
- Therapeutics. Pharmacology
RM1-950
Biochemistry
QD415-436
Subjects
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