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Vitamin D attenuates lung injury via stimulating epithelial repair, reducing epithelial cell apoptosis and inhibits TGF-β induced epithelial to mesenchymal transition
- Source :
- Biochemical pharmacology. 177
- Publication Year :
- 2020
-
Abstract
- Vitamin D regulates cell proliferation, inhibits cytokines release at sites of inflammation and reduces inflammatory responses. In this study, the aim was to investigate whether exogenous vitamin D attenuates LPS-induced lung injury via modulating epithelial cell proliferation, migration, apoptosis and epithelial mesenchymal transition (EMT). Murine and in vitro primary type II alveolar epithelial cell work were included in this study. In vivo, mice were mildly vitamin D deficient, 0.1, 1.5, 10 mg/kg 1,25(OH)2-vitamin D3 or 25(OH)-vitamin D3 was administrated by means of an intra-gastric injection for 14 days pre-intra-tracheal (IT) LPS, which remarkedly promoted alveolar epithelial type II cells proliferation, inhibited ATII cells apoptosis and inhibited EMT, with the outcome of attenuated LPS-induced lung injury. In vitro, vitamin D stimulated epithelial cell scratch wound repair, reduced primary ATII cells apoptosis as well. Vitamin D promoted primary human ATII cells proliferation through the PI3K/AKT signaling pathway and activation of vitamin D receptor (VDR). Moreover, vitamin D inhibited EMT in response to TGF-β, which was vitamin D receptor dependent. In conclusion, vitamin D attenuates lung injury via stimulating ATII cells proliferation and migration, reducing epithelial cell apoptosis and inhibits TGF-β induced EMT. Together, these results suggest that vitamin D has therapeutic potential for the resolution of ARDS.
- Subjects :
- 0301 basic medicine
Lipopolysaccharides
Male
Epithelial-Mesenchymal Transition
Inflammation
Apoptosis
Lung injury
Biochemistry
Calcitriol receptor
03 medical and health sciences
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Transforming Growth Factor beta
medicine
Vitamin D and neurology
Animals
Humans
Epithelial–mesenchymal transition
Vitamin D
PI3K/AKT/mTOR pathway
Cells, Cultured
Cell Proliferation
Pharmacology
Respiratory Distress Syndrome
Cell growth
Chemistry
Lung Injury
respiratory system
Middle Aged
Mice, Inbred C57BL
030104 developmental biology
030220 oncology & carcinogenesis
Alveolar Epithelial Cells
Cancer research
Receptors, Calcitriol
Female
medicine.symptom
Signal Transduction
Subjects
Details
- ISSN :
- 18732968
- Volume :
- 177
- Database :
- OpenAIRE
- Journal :
- Biochemical pharmacology
- Accession number :
- edsair.doi.dedup.....ccb120618d8caeacb79b1a9254d9eca8