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-2016 Volume 14 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-2016 Volume 14 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

Rab5a‑mediated autophagy regulates the phenotype and behavior of vascular smooth muscle cells

  • Authors:
    • Jin‑Yun Tan
    • Luo‑Qi Jia
    • Wei‑Hao Shi
    • Qing He
    • Lei Zhu
    • Bo Yu
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Huashan Hospital of Fudan University, Shanghai 200040, P.R. China, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, P.R. China, Department of Surgery, Pudong Hospital of Fudan University, Shanghai 201399, P.R. China
    Copyright: © Tan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4445-4453
    |
    Published online on: September 26, 2016
       https://doi.org/10.3892/mmr.2016.5774
  • 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

Rab5a, a key member of the Rab family of GTPases, was determined to be a regulator of vascular smooth muscle cell (VSMC) proliferation and migration. However, the exact regulatory mechanism remains unclear. As Rab5a has been shown to be associated with autophagy, which is essential for the conversion of VSMCs from a contractile to a synthetic phenotype in order to prevent cell death due to oxidative stress. The present study hypothesized that autophagy may be responsible for the proliferation and migration of VSMCs via the Rab5a protein. The aim of the present study was to evaluate the effect of Rab5a on autophagy in VSMCs. The human aorta vascular smooth muscle cell line, T/G HA‑VSMCs, was treated with small interfering (si)RNA against Rab5a and/or platelet‑derived growth factor (PDGF). Following treatment, the phenotype transition of the VSMCs was evaluated by detecting the mRNA and protien expression levels of VSMC molecular markers using reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. In addition, autophagy in VSMCs was evaluated by western blotting for autophagy‑associated proteins, flow cytometry of acidic vesicular organelles, punctate fluorescence of microtubule associated protein light chain 3 and transmission electron microscopy of typical scattered double‑membrane vacuolar structures. Additionally, the proliferation, migration, cell cycle and apoptotic response of VSMCs were detected by sulforhodamine B assay, transwell assay and flow cytometry, respectively. The results revealed that transfection with siRNA against Rab5a led to a significant decrease in Rab5a protein expression, while the reduced expression trend of Rab5a was rescued by intervention with PDGF. Furthermore, cells transfected with siRNA against Rab5a inhibited the autophagy of VSMCs. Downregulated Rab5a inhibited the phenotype transition of VSMCs. Additionally, downregulated Rab5a led to slowed cell growth, decreased numbers of migrated cells, decreased numbers of cells at the G0‑G1 phase and a higher apoptosis rate. However, PDGF significantly rescued these phenomena caused by siRNA against Rab5a. These results indicated that Rab5a‑mediated autophagy may regulate the phenotype transition and cell behavior of VSMCs through the activation of the extracellular‑regulated kinase 1/2 signaling pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Owens GK, Kumar MS and Wamhoff BR: Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev. 84:767–801. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Pyle AL and Young PP: Atheromas feel the pressure: Biomechanical stress and atherosclerosis. Am J Pathol. 177:4–9. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Rudijanto A: The role of vascular smooth muscle cells on the pathogenesis of atherosclerosis. Acta Med Indones. 39:86–93. 2007.PubMed/NCBI

4 

Mack CP: Signaling mechanisms that regulate smooth muscle cell differentiation. Arterioscler Thromb Vasc Biol. 31:1495–1505. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Jordens I, Marsman M, Kuijl C and Neefjes J: Rab proteins, connecting transport and vesicle fusion. Traffic. 6:1070–1077. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Grosshans BL, Ortiz D and Novick P: Rabs and their effectors: Achieving specificity in membrane traffic. Proc Natl Acad Sci USA. 103:11821–11827. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Hutagalung AH and Novick PJ: Role of Rab GTPases in membrane traffic and cell physiology. Physiol Rev. 91:119–149. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Ravikumar B, Imarisio S, Sarkar S, O'Kane CJ and Rubinsztein DC: Rab5 modulates aggregation and toxicity of mutant huntingtin through macroautophagy in cell and fly models of Huntington disease. J Cell Sci. 121:1649–1660. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Yang PS, Yin PH, Tseng LM, Yang CH, Hsu CY, Lee MY, Horng CF and Chi CW: Rab5A is associated with axillary lymph node metastasis in breast cancer patients. Cancer Sci. 102:2172–2178. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Liu SS, Chen XM, Zheng HX, Shi SL and Li Y: Knockdown of Rab5a expression decreases cancer cell motility and invasion through integrin-mediated signaling pathway. J Biomed Sci. 18:582011. View Article : Google Scholar : PubMed/NCBI

11 

Zhao Z, Liu XF, Wu HC, Zou SB, Wang JY, Ni PH, Chen XH and Fan QS: Rab5a overexpression promoting ovarian cancer cell proliferation may be associated with APPL1-related epidermal growth factor signaling pathway. Cancer Sci. 101:1454–1462. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Fukui K, Tamura S, Wada A, Kamada Y, Igura T, Kiso S and Hayashi N: Expression of Rab5a in hepatocellular carcinoma: Possible involvement in epidermal growth factor signaling. Hepatol Res. 37:957–965. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Ma Z, Wang H, Wu L, Zhui L, Shi W, Ma D, Chen Z and Yu B: RNAi-mediated Rab5a suppression inhibits proliferation and migration of vascular smooth muscle cells. Acta Cardiol. 65:507–514. 2010.PubMed/NCBI

14 

Salabei JK, Cummins TD, Singh M, Jones SP, Bhatnagar A and Hill BG: PDGF-mediated autophagy regulates vascular smooth muscle cell phenotype and resistance to oxidative stress. Biochem J. 451:375–388. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Butoi E, Gan AM and Manduteanu I: Molecular and functional interactions among monocytes/macrophages and smooth muscle cells and their relevance for atherosclerosis. Crit Rev Eukaryot Gene Expr. 24:341–355. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Garat C, Van Putten V, Refaat ZA, Dessev C, Han SY and Nemenoff RA: Induction of smooth muscle alpha-actin in vascular smooth muscle cells by arginine vasopressin is mediated by c-Jun amino-terminal kinases and p38 mitogen-activated protein kinase. J Biol Chem. 275:22537–22543. 2000. View Article : Google Scholar : PubMed/NCBI

18 

Hautmann MB, Thompson MM, Swartz EA, Olson EN and Owens GK: Angiotensin II-induced stimulation of smooth muscle alpha-actin expression by serum response factor and the homeodomain transcription factor MHox. Circ Res. 81:600–610. 1997. View Article : Google Scholar : PubMed/NCBI

19 

Wang L, Zheng J, Du Y, Huang Y, Li J, Liu B, Liu CJ, Zhu Y, Gao Y, Xu Q, et al: Cartilage oligomeric matrix protein maintains the contractile phenotype of vascular smooth muscle cells by interacting with alpha(7)beta(1) integrin. Circ Res. 106:514–525. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Su WC, Chao TC, Huang YL, Weng SC, Jeng KS and Lai MM: Rab5 and class III phosphoinositide 3-kinase Vps34 are involved in hepatitis C virus NS4B-induced autophagy. J Virol. 85:10561–10571. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Myllärniemi M, Calderon L, Lemström K, Buchdunger E and Häyry P: Inhibition of platelet-derived growth factor receptor tyrosine kinase inhibits vascular smooth muscle cell migration and proliferation. FASEB J. 11:1119–1126. 1997.PubMed/NCBI

22 

Yu JC, Lokker NA, Hollenbach S, Apatira M, Li J, Betz A, Sedlock D, Oda S, Nomoto Y, Matsuno K, et al: Efficacy of the novel selective platelet-derived growth factor receptor antagonist CT52923 on cellular proliferation, migration, and suppression of neointima following vascular injury. J Pharmacol Exp Ther. 298:1172–1178. 2001.PubMed/NCBI

23 

Levine B and Klionsky DJ: Development by self-digestion: Molecular mechanisms and biological functions of autophagy. Dev Cell. 6:463–477. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Du J, Teng RJ, Guan T, Eis A, Kaul S, Konduri GG and Shi Y: Role of autophagy in angiogenesis in aortic endothelial cells. Am J Physiol Cell Physiol. 302:C383–C391. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Slevin M, Krupinski J, Rovira N, Turu M, Luque A, Baldellou M, Sanfeliu C, de Vera N and Badimon L: Identification of pro-angiogenic markers in blood vessels from stroked-affected brain tissue using laser-capture microdissection. BMC Genomics. 10:1132009. View Article : Google Scholar : PubMed/NCBI

26 

Zhan Z, Xie X, Cao H, Zhou X, Zhang XD, Fan H and Liu Z: Autophagy facilitates TLR4-and TLR3-triggered migration and invasion of lung cancer cells through the promotion of TRAF6 ubiquitination. Autophagy. 10:257–268. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Lum JJ, DeBerardinis RJ and Thompson CB: Autophagy in metazoans: Cell survival in the land of plenty. Nat Rev Mol Cell Biol. 6:439–448. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Platini F, Pérez-Tomás R, Ambrosio S and Tessitore L: Understanding autophagy in cell death control. Curr Pharm Des. 16:101–113. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Shen S, Kepp O, Michaud M, Martins I, Minoux H, Métivier D, Maiuri MC, Kroemer RT and Kroemer G: Association and dissociation of autophagy, apoptosis and necrosis by systematic chemical study. Oncogene. 30:4544–4556. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Amaravadi RK: Autophagy-induced tumor dormancy in ovarian cancer. J Clin Invest. 118:3837–3840. 2008.PubMed/NCBI

31 

Hsieh AC, Liu Y, Edlind MP, Ingolia NT, Janes MR, Sher A, Shi EY, Stumpf CR, Christensen C, Bonham MJ, et al: The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature. 485:55–61. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Saiki S, Sasazawa Y, Imamichi Y, Kawajiri S, Fujimaki T, Tanida I, Kobayashi H, Sato F, Sato S, Ishikawa K, et al: Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. Autophagy. 7:176–187. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Wang RC, Wei Y, An Z, Zou Z, Xiao G, Bhagat G, White M, Reichelt J and Levine B: Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation. Science. 338:956–959. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Shaul YD and Seger R: The MEK/ERK cascade: From signaling specificity to diverse functions. Biochim Biophys Acta. 1773:1213–1226. 2007. View Article : Google Scholar : PubMed/NCBI

35 

Wang J, Whiteman MW, Lian H, Wang G, Singh A, Huang D and Denmark T: A non-canonical MEK/ERK signaling pathway regulates autophagy via regulating Beclin 1. J Biol Chem. 284:21412–21424. 2009. View Article : Google Scholar : PubMed/NCBI

36 

Cagnol S and Chambard JC: ERK and cell death: Mechanisms of ERK-induced cell death-apoptosis, autophagy and senescence. FEBS J. 277:2–21. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Tan JY, Jia LQ, Shi WH, He Q, Zhu L and Yu B: Rab5a‑mediated autophagy regulates the phenotype and behavior of vascular smooth muscle cells. Mol Med Rep 14: 4445-4453, 2016.
APA
Tan, J., Jia, L., Shi, W., He, Q., Zhu, L., & Yu, B. (2016). Rab5a‑mediated autophagy regulates the phenotype and behavior of vascular smooth muscle cells. Molecular Medicine Reports, 14, 4445-4453. https://doi.org/10.3892/mmr.2016.5774
MLA
Tan, J., Jia, L., Shi, W., He, Q., Zhu, L., Yu, B."Rab5a‑mediated autophagy regulates the phenotype and behavior of vascular smooth muscle cells". Molecular Medicine Reports 14.5 (2016): 4445-4453.
Chicago
Tan, J., Jia, L., Shi, W., He, Q., Zhu, L., Yu, B."Rab5a‑mediated autophagy regulates the phenotype and behavior of vascular smooth muscle cells". Molecular Medicine Reports 14, no. 5 (2016): 4445-4453. https://doi.org/10.3892/mmr.2016.5774
Copy and paste a formatted citation
x
Spandidos Publications style
Tan JY, Jia LQ, Shi WH, He Q, Zhu L and Yu B: Rab5a‑mediated autophagy regulates the phenotype and behavior of vascular smooth muscle cells. Mol Med Rep 14: 4445-4453, 2016.
APA
Tan, J., Jia, L., Shi, W., He, Q., Zhu, L., & Yu, B. (2016). Rab5a‑mediated autophagy regulates the phenotype and behavior of vascular smooth muscle cells. Molecular Medicine Reports, 14, 4445-4453. https://doi.org/10.3892/mmr.2016.5774
MLA
Tan, J., Jia, L., Shi, W., He, Q., Zhu, L., Yu, B."Rab5a‑mediated autophagy regulates the phenotype and behavior of vascular smooth muscle cells". Molecular Medicine Reports 14.5 (2016): 4445-4453.
Chicago
Tan, J., Jia, L., Shi, W., He, Q., Zhu, L., Yu, B."Rab5a‑mediated autophagy regulates the phenotype and behavior of vascular smooth muscle cells". Molecular Medicine Reports 14, no. 5 (2016): 4445-4453. https://doi.org/10.3892/mmr.2016.5774
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