Vitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin–angiotensin system in the lung
| Autor: | Xue Li, Yue Sun, Jianjun Chang, Yan Chun Li, Zhe Xun, Hongguang Nie, Xinzhi Wei, Weicheng Liu, Jie Du, Xin Ge |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Paricalcitol
medicine.medical_specialty Angiotensin receptor Pulmonary Fibrosis Science Angiotensinogen Diseases Pathogenesis Lung injury vitamin D deficiency Losartan Receptor Angiotensin Type 1 Article Renin-Angiotensin System Idiopathic pulmonary fibrosis Bleomycin Mice Endocrinology Transforming Growth Factor beta Internal medicine Pulmonary fibrosis Renin medicine Vitamin D and neurology Animals Vitamin D Lung Mice Knockout Multidisciplinary business.industry Angiotensin II respiratory system medicine.disease respiratory tract diseases Mice Inbred C57BL Disease Models Animal Ergocalciferols Medicine business Angiotensin II Type 1 Receptor Blockers medicine.drug |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Idiopathic pulmonary fibrosis (IPF) is a severe disorder leading to progressive and irreversible loss of pulmonary function. In this study we investigated the anti-fibrotic effect of vitamin D using a mouse model of IPF. Lung fibrosis was induced with bleomycin in vitamin D-sufficient and vitamin D-deficient C57BL/6 mice. We found that treatment with active vitamin D analog paricalcitol prevented mouse body weight loss and alleviated lung fibrosis, whereas vitamin D deficiency severely aggravated lung injury. At the molecular level, paricalcitol treatment suppressed the induction of fibrotic inducer TGF-β and extracellular matrix proteins α-SMA, collagen type I and fibronectin in the lung, whereas vitamin D deficiency exacerbated the induction of these proteins. Interestingly, bleomycin treatment activated the local renin–angiotensin system (RAS) in the lung, manifested by the induction of renin, angiotensinogen, angiotensin II and angiotensin receptor type 1 (AT1R). Paricalcitol treatment suppressed the induction of these RAS components, whereas vitamin D deficiency enhanced the activation of the lung RAS. We also showed that treatment of bleomycin-induced vitamin D-deficient mice with AT1R antagonist losartan relieved weight loss, substantially ameliorated lung fibrosis and markedly blocked TGF-β induction in the lung. Moreover, we demonstrated that in lung fibroblast cultures, TGF-β and angiotensin II synergistically induced TGF-β, AT1R, α-SMA, collagen type I and fibronectin, whereas 1,25-dihydroxyvitamin D markedly suppressed the induction of these fibrotic markers. Collectively, these observations strongly suggest that vitamin D mitigates lung fibrosis by blocking the activation of the lung RAS in this mouse model of IPF. |
| Databáze: | OpenAIRE |
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