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
June-2018 Volume 17 Issue 6

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
June-2018 Volume 17 Issue 6

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

Prohibitin and the extracellular matrix are upregulated in murine alveolar epithelial cells with LPS‑induced acute injury

  • Authors:
    • Feng Zhang
    • Dejun Fan
    • Xiao‑Neng Mo
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, The Sixth Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510655, P.R. China, Department of Gastrointestinal Endoscopy, The Sixth Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510655, P.R. China
  • Pages: 7769-7773
    |
    Published online on: March 28, 2018
       https://doi.org/10.3892/mmr.2018.8808
  • 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

Inflammation of epithelial and endothelial cells accelerates the progress of acute lung injury (ALI), and pulmonary fibrosis is the leading cause of mortality in patients with acute respiratory distress syndrome. Interleukin‑6 (IL‑6) is a pleiotropic cytokine implicated in the pathogenesis of a number of immune‑mediated disorders, and is involved in pulmonary fibrosis. Prohibitin (PHB) is a highly conserved protein implicated in various cellular functions, including proliferation, apoptosis, tumor suppression, transcription and mitochondrial protein folding. PHB was identified to be associated with a variety of pulmonary diseases, including pulmonary fibrosis. Based on the lipopolysaccharide (LPS)‑induced cell model of ALI, the present study examined the expression of PHB and the extracellular matrix (ECM) in the process of pulmonary inflammation. MLE‑12 cells were divided into 2 groups: The control group was administered sterile PBS; the treatment group was administered 500 ng/ml LPS for 12 h. The mRNA expression of IL‑6 in the treatment group was significantly upregulated compared with the control group (P<0.05). The protein expression of IL‑6 in the treatment group was markedly increased compared with the control group (P<0.05). ECM components, including collagen‑IV and fibronectin, in the treatment group were markedly increased when compared with the control group (P<0.05). The mRNA and protein expression levels of PHB1 and PHB2 were significantly upregulated following treatment with LPS (both P<0.05). The present study identified that PHB and ECM component levels increased in the LPS‑induced ALI cell model, and further investigations may be performed to verify the detailed mechanism.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Luh SP and Chiang CH: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): The mechanism, present strategies and future perspectives of therapies. J Zhejiang Univ Sci B. 8:60–69. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Matthay MA, Ware LB and Zimmerman GA: The acute respiratory distress syndrome. J Clin Invest. 122:2731–2740. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Tomashefski JF Jr: Pulmonary pathology of acute respiratory distress syndrome. Clin Chest Med. 21:435–466. 2000. View Article : Google Scholar : PubMed/NCBI

4 

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

5 

Orme JJ, Romney JS, Hopkins RO, Pope D, Chan KJ, Thomsen G, Crapo RO and Weaver LK: Pulmonary function and health-related quality of life in survivors of acute respiratory distress syndrome. Am J Respir Crit Care Med. 167:690–694. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Chida M, Ono S, Hoshikawa Y and Kondo T: Subclinical idiopathic pulmonary fibrosis is also a risk factor of postoperative acute respiratory distress syndrome following thoracic surgery. Eur J Cardiothorac Surg. 34:878–881. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Fukuda Y, Ishizaki M, Masuda Y, Kimura G, Kawanami O and Masugi Y: The role of intraalveolar fibrosis in the process of pulmonary structural remodeling in patients with diffuse alveolar damage. Am J Pathol. 126:171–182. 1987.PubMed/NCBI

8 

Lin P: Targeting interleukin-6 for noninfectious uveitis. Clin Ophthalmol. 9:1697–1702. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Rose-John S: The soluble interleukin-6 receptor and related proteins. Best Pract Res Clin Endocrinol Metab. 29:787–797. 2015. View Article : Google Scholar : PubMed/NCBI

10 

De Lauretis A, Sestini P, Pantelidis P, Hoyles R, Hansell DM, Goh NS, Zappala CJ, Visca D, Maher TM, Denton CP, et al: Serum interleukin 6 is predictive of early functional decline and mortality in interstitial lung disease associated with systemic sclerosis. J Rheumatol. 40:435–446. 2013. View Article : Google Scholar : PubMed/NCBI

11 

O'Donoghue RJ, Knight DA, Richards CD, Prêle CM, Lau HL, Jarnicki AG, Jones J, Bozinovski S, Vlahos R, Thiem S, et al: Genetic partitioning of interleukin-6 signalling in mice dissociates Stat3 from Smad3-mediated lung fibrosis. EMBO Mol Med. 4:939–951. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Yoshizaki A, Yanaba K, Ogawa A, Asano Y, Kadono T and Sato S: Immunization with DNA topoisomerase I and Freund's complete adjuvant induces skin and lung fibrosis and autoimmunity via interleukin-6 signaling. Arthritis Rheum. 63:3575–3585. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Snedden WA and Fromm H: Characterization of the plant homologue of prohibitin, a gene associated with antiproliferative activity in mammalian cells. Plant Mol Biol. 33:753–756. 1997. View Article : Google Scholar : PubMed/NCBI

14 

Merkwirth C and Langer T: Prohibitin function within mitochondria: Essential roles for cell proliferation and cristae morphogenesis. Biochim Biophys Acta. 1793:27–32. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Koushyar S, Jiang WG and Dart DA: Unveiling the potential of prohibitin in cancer. Cancer Lett. 369:316–322. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Peng YT, Chen P, Ouyang RY and Song L: Multifaceted role of prohibitin in cell survival and apoptosis. Apoptosis. 20:1135–1149. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Sharma A and Qadri A: Vi polysaccharide of Salmonella typhi targets the prohibitin family of molecules in intestinal epithelial cells and suppresses early inflammatory responses. Proc Natl Acad Sci USA. 101:17492–17497. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Theiss AL, Idell RD, Srinivasan S, Klapproth JM, Jones DP, Merlin D and Sitaraman SV: Prohibitin protects against oxidative stress in intestinal epithelial cells. FASEB J. 21:197–206. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Gamble SC, Chotai D, Odontiadis M, Dart DA, Brooke GN, Powell SM, Reebye V, Varela-Carver A, Kawano Y, Waxman J and Bevan CL: Prohibitin, a protein downregulated by androgens, represses androgen receptor activity. Oncogene. 26:1757–1768. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Theiss AL and Sitaraman SV: The role and therapeutic potential of prohibitin in disease. Biochim Biophys Acta. 1813:1137–1143. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Theiss AL, Vijay-Kumar M, Obertone TS, Jones DP, Hansen JM, Gewirtz AT, Merlin D and Sitaraman SV: Prohibitin is a novel regulator of antioxidant response that attenuates colonic inflammation in mice. Gastroenterology. 137(199–208): 208.e1–6. 2009.

22 

Soulitzis N, Neofytou E, Psarrou M, Anagnostis A, Tavernarakis N, Siafakas N and Tzortzaki EG: Downregulation of lung mitochondrial prohibitin in COPD. Respir Med. 106:954–961. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Agrawal T, Gupta GK and Agrawal DK: Vitamin D deficiency decreases the expression of VDR and prohibitin in the lungs of mice with allergic airway inflammation. Exp Mol Pathol. 93:74–81. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Ko KS, Tomasi ML, Iglesias-Ara A, French BA, French SW, Ramani K, Lozano JJ, Oh P, He L, Stiles BL, et al: Liver-specific deletion of prohibitin 1 results in spontaneous liver injury, fibrosis and hepatocellular carcinoma in mice. Hepatology. 52:2096–2108. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Zhou TB, Qin YH, Lei FY, Huang WF and Drummen GP: Prohibitin attenuates oxidative stress and extracellular matrix accumulation in renal interstitial fibrosis disease. PLoS One. 8:e771872013. View Article : Google Scholar : PubMed/NCBI

26 

Sanchez-Quiles V, Segura V, Bigaud E, He B, O'Malley BW, Santamaría E, Prieto J and Corrales FJ: Prohibitin-1 deficiency promotes inflammation and increases sensitivity to liver injury. J Proteomics. 75:5783–5792. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Hu X, Tian Y, Qu S, Cao Y, Li S, Zhang W, Zhang Z, Zhang N and Fu Y: Protective effect of TM6 on LPS-induced acute lung injury in mice. Sci Rep. 7:5722017. View Article : Google Scholar : PubMed/NCBI

28 

Zhao J, He D, Su Y, Berdyshev E, Chun J, Natarajan V and Zhao Y: Lysophosphatidic acid receptor 1 modulates lipopolysaccharide-induced inflammation in alveolar epithelial cells and murine lungs. Am J Physiol Lung Cell Mol Physiol. 301:L547–L556. 2011. View Article : Google Scholar : PubMed/NCBI

29 

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

30 

Rocco PR, Dos SC and Pelosi P: Lung parenchyma remodeling in acute respiratory distress syndrome. Minerva Anestesiol. 75:730–740. 2009.PubMed/NCBI

31 

Burnham EL, Janssen WJ, Riches DW, Moss M and Downey GP: The fibroproliferative response in acute respiratory distress syndrome: Mechanisms and clinical significance. Eur Respir J. 43:276–285. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Cottin V: Interstitial lung disease. Eur Respir Rev. 22:26–32. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Chapman HA: Epithelial-mesenchymal interactions in pulmonary fibrosis. Annu Rev Physiol. 73:413–435. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Dong WW, Zhang YQ, Zhu XY, Mao YF, Sun XJ, Liu YJ and Jiang L: Protective effects of hydrogen-rich saline against lipopolysaccharide-induced alveolar epithelial-to-mesenchymal transition and pulmonary fibrosis. Med Sci Monit. 23:2357–2364. 2017. View Article : Google Scholar : PubMed/NCBI

35 

He D, Su Y, Usatyuk PV, Spannhake EW, Kogut P, Solway J, Natarajan V and Zhao Y: Lysophosphatidic acid enhances pulmonary epithelial barrier integrity and protects endotoxin-induced epithelial barrier disruption and lung injury. J Biol Chem. 284:24123–24132. 2009. View Article : Google Scholar : PubMed/NCBI

36 

Zhao D, Ding R, Mao Y, Wang L, Zhang Z and Ma X: Heparin rescues sepsis-associated acute lung injury and lethality through the suppression of inflammatory responses. Inflammation. 35:1825–1832. 2012. View Article : Google Scholar : PubMed/NCBI

37 

Zhu T, Wang DX, Zhang W, Liao XQ, Guan X, Bo H, Sun JY, Huang NW, He J, Zhang YK, et al: Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-kappaB. PLoS One. 8:e564072013. View Article : Google Scholar : PubMed/NCBI

38 

Zhou TB, Qin YH, Li ZY, Xu HL, Zhao YJ and Lei FY: All-trans retinoic acid treatment is associated with prohibitin expression in renal interstitial fibrosis rats. Int J Mol Sci. 13:2769–2782. 2012. View Article : Google Scholar : PubMed/NCBI

39 

Theiss AL, Obertone TS, Merlin D and Sitaraman SV: Interleukin-6 transcriptionally regulates prohibitin expression in intestinal epithelial cells. J Biol Chem. 282:12804–12812. 2007. View Article : Google Scholar : PubMed/NCBI

40 

Yuan C, Chen WX, Zhu JS, Chen NW, Lu YM, Ou YX and Chen HQ: IL-10 treatment is associated with prohibitin expression in the Crohn's disease intestinal fibrosis mouse model. Mediators Inflamm. 2013:6171452013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang F, Fan D and Mo XN: Prohibitin and the extracellular matrix are upregulated in murine alveolar epithelial cells with LPS‑induced acute injury. Mol Med Rep 17: 7769-7773, 2018.
APA
Zhang, F., Fan, D., & Mo, X. (2018). Prohibitin and the extracellular matrix are upregulated in murine alveolar epithelial cells with LPS‑induced acute injury. Molecular Medicine Reports, 17, 7769-7773. https://doi.org/10.3892/mmr.2018.8808
MLA
Zhang, F., Fan, D., Mo, X."Prohibitin and the extracellular matrix are upregulated in murine alveolar epithelial cells with LPS‑induced acute injury". Molecular Medicine Reports 17.6 (2018): 7769-7773.
Chicago
Zhang, F., Fan, D., Mo, X."Prohibitin and the extracellular matrix are upregulated in murine alveolar epithelial cells with LPS‑induced acute injury". Molecular Medicine Reports 17, no. 6 (2018): 7769-7773. https://doi.org/10.3892/mmr.2018.8808
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang F, Fan D and Mo XN: Prohibitin and the extracellular matrix are upregulated in murine alveolar epithelial cells with LPS‑induced acute injury. Mol Med Rep 17: 7769-7773, 2018.
APA
Zhang, F., Fan, D., & Mo, X. (2018). Prohibitin and the extracellular matrix are upregulated in murine alveolar epithelial cells with LPS‑induced acute injury. Molecular Medicine Reports, 17, 7769-7773. https://doi.org/10.3892/mmr.2018.8808
MLA
Zhang, F., Fan, D., Mo, X."Prohibitin and the extracellular matrix are upregulated in murine alveolar epithelial cells with LPS‑induced acute injury". Molecular Medicine Reports 17.6 (2018): 7769-7773.
Chicago
Zhang, F., Fan, D., Mo, X."Prohibitin and the extracellular matrix are upregulated in murine alveolar epithelial cells with LPS‑induced acute injury". Molecular Medicine Reports 17, no. 6 (2018): 7769-7773. https://doi.org/10.3892/mmr.2018.8808
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