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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Li, Se-Ruo Tan, Zhu-Xia Chen, Yuan-Hua Hu, Biao Zhang, Cheng Wang, Hua Zhao, Hui Xu, De-Xiang |
| Abstract | Background Our earlier report indicated that active vitamin D3 inhibited epithelial-mesenchymal transition (EMT) in bleomycin (BLM)-induced pulmonary fibrosis. The objective of this study was to further investigate whether vitamin D deficiency exacerbates BLM-induced pulmonary fibrosis. Methods This study consists of two independent experiments. Experiment 1, male mice were fed with vitamin D deficient (VDD) fodder. Experiment 2, Cyp27b1+/+, Cyp27b1+/− and Cyp27b1−/− mice were fed with standard diet. For pulmonary fibrosis, mice were intratracheally instilled with a single dose of BLM (1.5 mg/kg). Serum 25(OH) D level was measured. Pulmonary collagen deposition was assessed by Sirius red staining. EMT was measured and transforming growth factor-beta (TGF-β)/Smad3 signaling was evaluated in the lungs of BLM-treated mice. Results The relative weight of lungs was elevated in BLM-treated mice. Col1α1 and Col1α2, two collagen protein genes, were upregulated, and collagen deposition, as determined by Sirius red staining, was observed in the lungs of BLM-treated mice. E-cadherin, an epithelial marker, was downregulated. By contrast, vimentin and α-SMA, two EMT markers, were upregulated in the lungs of BLM-treated mice. Pulmonary TGF-β/Smad3 signaling was activated in BLM-induced lung fibrosis. Further analysis showed that feeding VDD diet, leading to vitamin D deficiency, aggravated elevation of BLM-induced relative lung weight. Moreover, feeding VDD diet aggravated BLM-induced TGF-β/Smad3 activation and subsequent EMT in the lungs. In addition, feeding VDD diet exacerbated BLM-induced pulmonary fibrosis. Additional experiment showed that Cyp27b1 gene knockout, leading to active vitamin D3 deficiency, exacerbated BLM-induced pulmonary fibrosis. Moreover, Cyp27b1 gene knockout aggravated pulmonary TGF-β/Smad2/3 activation and subsequent EMT in BLM-induced lung fibrosis. Conclusion Vitamin D deficiency exacerbates BLM-induced pulmonary fibrosis partially through aggravating TGF-β/Smad2/3-mediated EMT in the lungs. |
| Related Links | https://respiratory-research.biomedcentral.com/counter/pdf/10.1186/s12931-019-1232-6.pdf |
| Ending Page | 11 |
| Page Count | 11 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s12931-019-1232-6 |
| Journal | Respiratory Research |
| Issue Number | 1 |
| Volume Number | 20 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2019-11-27 |
| Access Restriction | Open |
| Subject Keyword | Pneumology Respiratory System Pulmonary fibrosis Vitamin D deficiency Epithelial-mesenchymal transition Bleomycin Mice Pneumology/Respiratory System |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pulmonary and Respiratory Medicine |
| Journal Impact Factor | 4.7/2023 |
| 5-Year Journal Impact Factor | 5.3/2023 |
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