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The protective role of vitamin D3 in a murine model of asthma via the suppression of TGF-β/Smad signaling and activation of the Nrf2/HO-1 pathway

  • Authors:
    • Zhihui Wang
    • Haitao Zhang
    • Xiaohan Sun
    • Lihong Ren
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Internal Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2389-2396
    |
    Published online on: July 27, 2016
       https://doi.org/10.3892/mmr.2016.5563
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Abstract

Asthma is a common worldwide health burden, the prevalence of which is increasing. Recently, the biologically active form of vitamin D3, 1,25-dihydroxyvitamin D3, has been reported to have a protective role in murine asthma; however, the molecular mechanisms by which vitamin D3 attenuates asthma‑associated airway injury remain elusive. In the present study, BALB/c mice were sensitized to ovalbumin (OVA) and were administered 100 ng 1,25-dihydroxyvitamin D3 (intraperitoneal injection) 30 min prior to each airway challenge. The inflammatory responses were measured by ELISA, airway damage was analyzed by hematoxylin and eosin staining, airway remodeling was analyzed by Masson staining and periodic acid‑Schiff staining, markers of oxidative stress were measured by commercial kits, and the expression levels of α‑smooth muscle actin (α-SMA) and the activity of the NF‑E2‑related factor 2 (Nrf2)/heme oxygenase‑1 (HO‑1) and the transforming growth factor‑β (TGF‑β)/Smad signaling pathways were measured by immunohistochemistry and western blotting. The results demonstrated that OVA‑induced airway inflammation and immunoglobulin E overexpression were significantly reduced by vitamin D3 treatment. In addition, treatment with vitamin D3 decreased α‑SMA expression, collagen deposition and goblet cell hyperplasia, and inhibited TGF‑β/Smad signaling in the asthmatic airway. The upregulated levels of malondialdehyde, and the reduced activities of superoxide dismutase and glutathione in OVA‑challenged mice were also markedly restored following vitamin D3 treatment. Furthermore, treatment with vitamin D3 enhanced activation of the Nrf2/HO‑1 pathway in the airways of asthmatic mice. In conclusion, these findings suggest that vitamin D3 may protect airways from asthmatic damage via the suppression of TGF‑β/Smad signaling and activation of the Nrf2/HO‑1 pathway; however, these protective effects were shown to be accompanied by hypercalcemia.
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Copy and paste a formatted citation
Spandidos Publications style
Wang Z, Zhang H, Sun X and Ren L: The protective role of vitamin D3 in a murine model of asthma via the suppression of TGF-β/Smad signaling and activation of the Nrf2/HO-1 pathway. Mol Med Rep 14: 2389-2396, 2016.
APA
Wang, Z., Zhang, H., Sun, X., & Ren, L. (2016). The protective role of vitamin D3 in a murine model of asthma via the suppression of TGF-β/Smad signaling and activation of the Nrf2/HO-1 pathway. Molecular Medicine Reports, 14, 2389-2396. https://doi.org/10.3892/mmr.2016.5563
MLA
Wang, Z., Zhang, H., Sun, X., Ren, L."The protective role of vitamin D3 in a murine model of asthma via the suppression of TGF-β/Smad signaling and activation of the Nrf2/HO-1 pathway". Molecular Medicine Reports 14.3 (2016): 2389-2396.
Chicago
Wang, Z., Zhang, H., Sun, X., Ren, L."The protective role of vitamin D3 in a murine model of asthma via the suppression of TGF-β/Smad signaling and activation of the Nrf2/HO-1 pathway". Molecular Medicine Reports 14, no. 3 (2016): 2389-2396. https://doi.org/10.3892/mmr.2016.5563
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Z, Zhang H, Sun X and Ren L: The protective role of vitamin D3 in a murine model of asthma via the suppression of TGF-β/Smad signaling and activation of the Nrf2/HO-1 pathway. Mol Med Rep 14: 2389-2396, 2016.
APA
Wang, Z., Zhang, H., Sun, X., & Ren, L. (2016). The protective role of vitamin D3 in a murine model of asthma via the suppression of TGF-β/Smad signaling and activation of the Nrf2/HO-1 pathway. Molecular Medicine Reports, 14, 2389-2396. https://doi.org/10.3892/mmr.2016.5563
MLA
Wang, Z., Zhang, H., Sun, X., Ren, L."The protective role of vitamin D3 in a murine model of asthma via the suppression of TGF-β/Smad signaling and activation of the Nrf2/HO-1 pathway". Molecular Medicine Reports 14.3 (2016): 2389-2396.
Chicago
Wang, Z., Zhang, H., Sun, X., Ren, L."The protective role of vitamin D3 in a murine model of asthma via the suppression of TGF-β/Smad signaling and activation of the Nrf2/HO-1 pathway". Molecular Medicine Reports 14, no. 3 (2016): 2389-2396. https://doi.org/10.3892/mmr.2016.5563
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