Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
November-2017 Volume 16 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2017 Volume 16 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Vitamin D alleviates lipopolysaccharide‑induced acute lung injury via regulation of the renin‑angiotensin system

  • Authors:
    • Jun Xu
    • Jialai Yang
    • Jian Chen
    • Qingli Luo
    • Qiu Zhang
    • Hong Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Emergency Department, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Intensive Care Unit, Southside of Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui 230001, P.R. China, Anhui Provincial Laboratory of Pathogen Biology, Anhui Medical University, Hefei, Anhui 230022, P.R. China
    Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 7432-7438
    |
    Published online on: September 20, 2017
       https://doi.org/10.3892/mmr.2017.7546
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. ALI and ARDS result are associated with high mortality in patients. At present, no effective treatments for ALI and ARDS exist. It is established that vitamin D exhibits anti‑inflammatory effects, however, the specific effect of vitamin D on ALI remains largely unknown. The aim of the present study was to investigate whether, and by which mechanism, vitamin D alleviates lipopolysaccharide (LPS)‑induced ALI. The results demonstrated that a vitamin D agonist, calcitriol, exhibited a beneficial effect on LPS‑induced ALI in rats; calcitriol pretreatment significantly improved LPS‑induced lung permeability, as determined using Evans blue dye. Results from reverse transcription‑quantitative polymerase chain reaction, western blotting and ELISA analysis demonstrated that calcitriol also modulated the expression of members of the renin‑angiotensin system (RAS), including angiotensin (Ang) I‑converting enzymes (ACE and ACE2), renin and Ang II, which indicates that calcitriol may exert protective effects on LPS‑induced lung injury, at least partially, by regulating the balance between the expression of members of the RAS. The results of the present study may provide novel targets for the future treatment of ALI.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ and Hudson LD: Incidence and outcomes of acute lung injury. N Engl J Med. 353:1685–1693. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Phua J, Badia JR, Adhikari NK, Friedrich JO, Fowler RA, Singh JM, Scales DC, Stather DR, Li A, Jones A, et al: Has mortality from acute respiratory distress syndrome decreased over time? A systematic review. Am J Respir Crit Care Med. 179:220–227. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Matute-Bello G, Frevert CW and Martin TR: Animal models of acute lung injury. Am J Physiol Lung Cell Mol Physiol. 295:L379–L399. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Wheeler AP and Bernard GR: Acute lung injury and the acute respiratory distress syndrome: A clinical review. Lancet. 369:1553–1564. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Su X, Wang L, Song Y and Bai C: Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide. Intensive Care Med. 30:133–140. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, Dominguez CE and Jurutka PW: The nuclear vitamin D receptor: Biological and molecular regulatory properties revealed. J Bone Miner Res. 13:325–349. 1998. View Article : Google Scholar : PubMed/NCBI

7 

Hansdottir S, Monick MM, Hinde SL, Lovan N, Look DC and Hunninghake GW: Respiratory epithelial cells convert inactive vitamin D to its active form: Potential effects on host defense. J Immunol. 181:7090–7099. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Jeffery LE, Burke F, Mura M, Zheng Y, Qureshi OS, Hewison M, Walker LS, Lammas DA, Raza K and Sansom DM: 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J Immunol. 183:5458–5467. 2009. View Article : Google Scholar : PubMed/NCBI

9 

D'Alessio FR, Tsushima K, Aggarwal NR, West EE, Willett MH, Britos MF, Pipeling MR, Brower RG, Tuder RM, McDyer JF and King LS: CD4+CD25+Foxp3+ Tregs resolve experimental lung injury in mice and are present in humans with acute lung injury. J Clin Invest. 119:2898–2913. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Kong J, Zhu X, Shi Y, Liu T, Chen Y, Bhan I, Zhao Q, Thadhani R and Li YC: VDR attenuates acute lung injury by blocking Ang-2-Tie-2 pathway and renin-angiotensin system. Mol Endocrinol. 27:2116–2125. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G and Turner AJ: A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 275:33238–33243. 2000. View Article : Google Scholar : PubMed/NCBI

12 

Santos RA, Ferreira AJ, Verano-Braga T and Bader M: Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: New players of the renin-angiotensin system. J Endocrinol. 216:R1–R17. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, et al: Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 436:112–116. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Treml B, Neu N, Kleinsasser A, Gritsch C, Finsterwalder T, Geiger R, Schuster M, Janzek E, Loibner H, Penninger J and Loeckinger A: Recombinant angiotensin-converting enzyme 2 improves pulmonary blood flow and oxygenation in lipopolysaccharide-induced lung injury in piglets. Crit Care Med. 38:596–601. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Li Y, Zeng Z, Cao Y, Liu Y, Ping F, Liang M, Xue Y, Xi C, Zhou M and Jiang W: Angiotensin-converting enzyme 2 prevents lipopolysaccharide-induced rat acute lung injury via suppressing the ERK1/2 and NF-κB signaling pathways. Sci Rep. 6:279112016. View Article : Google Scholar : PubMed/NCBI

16 

Li YC, Qiao G, Uskokovic M, Xiang W, Zheng W and Kong J: Vitamin D: A negative endocrine regulator of the renin-angiotensin system and blood pressure. J Steroid Biochem Mol Biol 89–90. 1–392. 2004.

17 

Shi Y, Liu T, Li Y, Xing Y, Zhao X, Fu J and Xue X: Chronic vitamin D deficiency induces lung fibrosis through activation of the renin-angiotensin system. Sci Rep. 7:33122017. View Article : Google Scholar : PubMed/NCBI

18 

Zhou C, Lu F, Cao K, Xu D, Goltzman D and Miao D: Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin-angiotensin system in 1alpha-hydroxylase knockout mice. Kidney Int. 74:170–179. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Zhang H and Sun GY: Expression and regulation of AT1 receptor in rat lung microvascular endothelial cell. J Surg Res. 134:190–197. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Yang P, Gu H, Zhao Z, Wang W, Cao B, Lai C, Yang X, Zhang L, Duan Y, Zhang S, et al: Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury. Sci Rep. 4:70272014. View Article : Google Scholar : PubMed/NCBI

22 

Rey-Parra GJ, Vadivel A, Coltan L, Hall A, Eaton F, Schuster M, Loibner H, Penninger JM, Kassiri Z, Oudit GY and Thébaud B: Angiotensin converting enzyme 2 abrogates bleomycin-induced lung injury. J Mol Med (Berl). 90:637–647. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Borghi C, Boschi S, Ambrosioni E, Melandr G, Branzi A and Magnani B: Evidence of a partial escape of renin-angiotensin-aldosterone blockade in patients with acute myocardial infarction treated with ACE inhibitors. J Clin Pharmacol. 33:40–45. 1993. View Article : Google Scholar : PubMed/NCBI

24 

Ware LB and Matthay MA: The acute respiratory distress syndrome. N Engl J Med. 342:1334–1349. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Shi YY, Liu TJ, Fu JH, Xu W, Wu LL, Hou AN and Xue XD: Vitamin D/VDR signaling attenuates lipopolysaccharide-induced acute lung injury by maintaining the integrity of the pulmonary epithelial barrier. Mol Med Rep. 13:1186–1194. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Zhang M, Dong M, Liu W, Wang L, Luo Y, Li Z and Jin F: 1α,25-dihydroxyvitamin D3 ameliorates seawater aspiration-induced acute lung injury via NF-κB and RhoA/Rho kinase pathways. PLoS One. 9:e1045072014. View Article : Google Scholar : PubMed/NCBI

27 

Li YC, Kong J, Wei M, Chen ZF, Liu SQ and Cao LP: 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 110:229–238. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Ishii K, Takeuchi H, Fukunaga K, Hirano Y, Suda K, Hagiwara T, Miyasho T, Yamada S, Nakamura R, Takahashi T, et al: Attenuation of lipopolysaccharide-induced acute lung injury after (pro)renin receptor blockade. Exp Lung Res. 41:199–207. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Chen LN, Yang XH, Nissen DH, Chen YY, Wang LJ, Wang JH, Gao JL and Zhang LY: Dysregulated renin-angiotensin system contributes to acute lung injury caused by hind-limb ischemia-reperfusion in mice. Shock. 40:420–429. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Liu L, Qiu HB, Yang Y, Wang L, Ding HM and Li HP: Losartan, an antagonist of AT1 receptor for angiotensin II, attenuates lipopolysaccharide-induced acute lung injury in rat. Arch Biochem Biophys. 481:131–136. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Wang F, Xia ZF, Chen XL, Jia YT, Wang YJ and Ma B: Angiotensin II type-1 receptor antagonist attenuates LPS-induced acute lung injury. Cytokine. 48:246–253. 2009. View Article : Google Scholar : PubMed/NCBI

32 

Burrell LM, Johnston CI, Tikellis C and Cooper ME: ACE2, a new regulator of the renin-angiotensin system. Trends Endocrinol Metab. 15:166–169. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Shi Y, Zhang B, Chen XJ, Xu DQ, Wang YX, Dong HY, Ma SR, Sun RH, Hui YP and Li ZC: Osthole protects lipopolysaccharide-induced acute lung injury in mice by preventing down-regulation of angiotensin-converting enzyme 2. Eur J Pharm Sci. 48:819–824. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Zambelli V, Bellani G, Borsa R, Pozzi F, Grassi A, Scanziani M, Castiglioni V, Masson S, Decio A, Laffey JG, et al: Angiotensin-(1–7) improves oxygenation, while reducing cellular infiltrate and fibrosis in experimental acute respiratory distress syndrome. Intensive Care Med Exp. 3:442015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xu J, Yang J, Chen J, Luo Q, Zhang Q and Zhang H: Vitamin D alleviates lipopolysaccharide‑induced acute lung injury via regulation of the renin‑angiotensin system. Mol Med Rep 16: 7432-7438, 2017.
APA
Xu, J., Yang, J., Chen, J., Luo, Q., Zhang, Q., & Zhang, H. (2017). Vitamin D alleviates lipopolysaccharide‑induced acute lung injury via regulation of the renin‑angiotensin system. Molecular Medicine Reports, 16, 7432-7438. https://doi.org/10.3892/mmr.2017.7546
MLA
Xu, J., Yang, J., Chen, J., Luo, Q., Zhang, Q., Zhang, H."Vitamin D alleviates lipopolysaccharide‑induced acute lung injury via regulation of the renin‑angiotensin system". Molecular Medicine Reports 16.5 (2017): 7432-7438.
Chicago
Xu, J., Yang, J., Chen, J., Luo, Q., Zhang, Q., Zhang, H."Vitamin D alleviates lipopolysaccharide‑induced acute lung injury via regulation of the renin‑angiotensin system". Molecular Medicine Reports 16, no. 5 (2017): 7432-7438. https://doi.org/10.3892/mmr.2017.7546
Copy and paste a formatted citation
x
Spandidos Publications style
Xu J, Yang J, Chen J, Luo Q, Zhang Q and Zhang H: Vitamin D alleviates lipopolysaccharide‑induced acute lung injury via regulation of the renin‑angiotensin system. Mol Med Rep 16: 7432-7438, 2017.
APA
Xu, J., Yang, J., Chen, J., Luo, Q., Zhang, Q., & Zhang, H. (2017). Vitamin D alleviates lipopolysaccharide‑induced acute lung injury via regulation of the renin‑angiotensin system. Molecular Medicine Reports, 16, 7432-7438. https://doi.org/10.3892/mmr.2017.7546
MLA
Xu, J., Yang, J., Chen, J., Luo, Q., Zhang, Q., Zhang, H."Vitamin D alleviates lipopolysaccharide‑induced acute lung injury via regulation of the renin‑angiotensin system". Molecular Medicine Reports 16.5 (2017): 7432-7438.
Chicago
Xu, J., Yang, J., Chen, J., Luo, Q., Zhang, Q., Zhang, H."Vitamin D alleviates lipopolysaccharide‑induced acute lung injury via regulation of the renin‑angiotensin system". Molecular Medicine Reports 16, no. 5 (2017): 7432-7438. https://doi.org/10.3892/mmr.2017.7546
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team