Skip to main content
SpringerLink
Log in

Methods to Investigate the Roles of Progranulin in Angiogenesis Using In Vitro Strategies and Transgenic Mouse Models

  • Protocol
  • First Online:
Progranulin

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1806))

Abstract

Endothelial cells activate the expression of progranulin during angiogenesis. Here we discuss methods to investigate progranulin activity on endothelial cells in vitro and on aortic explants. We then discuss methods to generate transgenic mice in which progranulin expression is targeted to endothelial cells. These mice can be used to study the influence of progranulin on angiogenesis during development in vivo. The transgenic strategy summarized here could be readily adapted to investigate the roles of progranulin in other cell types and tissues by use of appropriate targeting vectors to drive the expression of progranulin in the cell type of choice.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Chung AS, Ferrara N (2011) Developmental and pathological angiogenesis. Annu Rev Cell Dev Biol 27:563–584. https://doi.org/10.1146/annurev-cellbio-092910-154002

    Article  PubMed  CAS  Google Scholar 

  2. Bao P, Kodra A, Tomic-Canic M, Golinko MS, Ehrlich HP, Brem H (2009) The role of vascular endothelial growth factor in wound healing. J Surg Res 153(2):347–358. https://doi.org/10.1016/j.jss.2008.04.023

    Article  PubMed  CAS  Google Scholar 

  3. Johnson KE, Wilgus TA (2014) Vascular endothelial growth factor and angiogenesis in the regulation of cutaneous wound repair. Adv Wound Care (New Rochelle) 3(10):647–661. https://doi.org/10.1089/wound.2013.0517

    Article  PubMed Central  Google Scholar 

  4. Andres AC, Djonov V (2010) The mammary gland vasculature revisited. J Mammary Gland Biol Neoplasia 15(3):319–328. https://doi.org/10.1007/s10911-010-9186-9

    Article  PubMed  Google Scholar 

  5. Demir R, Seval Y, Huppertz B (2007) Vasculogenesis and angiogenesis in the early human placenta. Acta Histochem 109(4):257–265. https://doi.org/10.1016/j.acthis.2007.02.008

    Article  PubMed  CAS  Google Scholar 

  6. Demir R, Yaba A, Huppertz B (2010) Vasculogenesis and angiogenesis in the endometrium during menstrual cycle and implantation. Acta Histochem 112(3):203–214. https://doi.org/10.1016/j.acthis.2009.04.004

    Article  PubMed  CAS  Google Scholar 

  7. Cheng R, Ma JX (2015) Angiogenesis in diabetes and obesity. Rev Endocr Metab Disord 16(1):67–75. https://doi.org/10.1007/s11154-015-9310-7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Martínez CE, Smith PC, Palma Alvarado VA (2015) The influence of platelet-derived products on angiogenesis and tissue repair: a concise update. Front Physiol 6(290). https://doi.org/10.3389/fphys.2015.00290

  9. Presta M, Dell’Era P, Mitola S, Moroni E, Ronca R, Rusnati M (2005) Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev 16(2):159–178. https://doi.org/10.1016/j.cytogfr.2005.01.004

    Article  CAS  Google Scholar 

  10. Mahabeleshwar GH, Feng W, Phillips DR, Byzova TV (2006) Integrin signaling is critical for pathological angiogenesis. J Exp Med 203(11):2495–2507. https://doi.org/10.1084/jem.20060807

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Brooks PC, Clark RA, Cheresh DA (1994) Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 264(5158):569–571

    Article  CAS  PubMed  Google Scholar 

  12. Daniel R, He Z, Carmichael KP, Halper J, Bateman A (2000) Cellular localization of gene expression for progranulin. J Histochem Cytochem 48(7):999–1009. https://doi.org/10.1177/002215540004800713

    Article  PubMed  CAS  Google Scholar 

  13. He Z, Ong CH, Halper J, Bateman A (2003) Progranulin is a mediator of the wound response. Nat Med 9(2):225–229. https://doi.org/10.1038/nm816

    Article  CAS  PubMed  Google Scholar 

  14. Daniel R, Daniels E, He Z, Bateman A (2003) Progranulin (acrogranin/PC cell-derived growth factor/granulin-epithelin precursor) is expressed in the placenta, epidermis, microvasculature, and brain during murine development. Dev Dyn 227(4):593–599. https://doi.org/10.1002/dvdy.10341

    Article  PubMed  CAS  Google Scholar 

  15. Desmarais JA, Cao M, Bateman A, Murphy BD (2008) Spatiotemporal expression pattern of progranulin in embryo implantation and placenta formation suggests a role in cell proliferation, remodeling, and angiogenesis. Reproduction 136(2):247–257. https://doi.org/10.1530/REP-08-0044

    Article  PubMed  CAS  Google Scholar 

  16. Davidson B, Alejandro E, Florenes VA, Goderstad JM, Risberg B, Kristensen GB, Trope CG, Kohn EC (2004) Granulin-epithelin precursor is a novel prognostic marker in epithelial ovarian carcinoma. Cancer 100(10):2139–2147. https://doi.org/10.1002/cncr.20219

    Article  PubMed  CAS  Google Scholar 

  17. Gonzalez EM, Mongiat M, Slater SJ, Baffa R, Iozzo RV (2003) A novel interaction between perlecan protein core and progranulin: potential effects on tumor growth. J Biol Chem 278(40):38113–38116. https://doi.org/10.1074/jbc.C300310200

    Article  PubMed  CAS  Google Scholar 

  18. Li LQ, Min LS, Jiang Q, Ping JL, Li J, Dai LC (2012) Progranulin expression in breast cancer with different intrinsic subtypes. Pathol Res Pract 208(4):210–216. https://doi.org/10.1016/j.prp.2012.02.001

    Article  PubMed  CAS  Google Scholar 

  19. Chen XY, Li JS, Liang QP, He DZ, Zhao J (2008) Expression of PC cell-derived growth factor and vascular endothelial growth factor in esophageal squamous cell carcinoma and their clinicopathologic significance. Chin Med J 121(10):881–886

    PubMed  CAS  Google Scholar 

  20. Wang M, Li G, Yin J, Lin T, Zhang J (2012) Progranulin overexpression predicts overall survival in patients with glioblastoma. Med Oncol 29(4):2423–2431. https://doi.org/10.1007/s12032-011-0131-6

    Article  PubMed  CAS  Google Scholar 

  21. Yang D, Wang LL, Dong TT, Shen YH, Guo XS, Liu CY, Liu J, Zhang P, Li J, Sun YP (2015) Progranulin promotes colorectal cancer proliferation and angiogenesis through TNFR2/Akt and ERK signaling pathways. Am J Cancer Res 5(10):3085–3097

    PubMed  PubMed Central  CAS  Google Scholar 

  22. Tangkeangsirisin W, Serrero G (2004) PC cell-derived growth factor (PCDGF/GP88, progranulin) stimulates migration, invasiveness and VEGF expression in breast cancer cells. Carcinogenesis 25(9):1587–1592. https://doi.org/10.1093/carcin/bgh171

    Article  PubMed  CAS  Google Scholar 

  23. Toh H, Cao M, Daniels E, Bateman A (2013) Expression of the growth factor progranulin in endothelial cells influences growth and development of blood vessels: a novel mouse model. PLoS One 8(5):e64989. https://doi.org/10.1371/journal.pone.0064989

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Kawase R, Ohama T, Matsuyama A, Matsuwaki T, Okada T, Yamashita T, Yuasa-Kawase M, Nakaoka H, Nakatani K, Inagaki M, Tsubakio-Yamamoto K, Masuda D, Nakagawa-Toyama Y, Nishida M, Ohmoto Y, Nishihara M, Komuro I, Yamashita S (2013) Deletion of progranulin exacerbates atherosclerosis in ApoE knockout mice. Cardiovasc Res 100(1):125–133. https://doi.org/10.1093/cvr/cvt178

    Article  CAS  PubMed  Google Scholar 

  25. Jackman K, Kahles T, Lane D, Garcia-Bonilla L, Abe T, Capone C, Hochrainer K, Voss H, Zhou P, Ding A, Anrather J, Iadecola C (2013) Progranulin deficiency promotes post-ischemic blood-brain barrier disruption. J Neurosci 33(50):19579–19589. https://doi.org/10.1523/JNEUROSCI.4318-13.2013

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Shakado S, Sakisaka S, Noguchi K, Yoshitake M, Harada M, Mimura Y, Sata M, Tanikawa K (1995) Effects of extracellular matrices on tube formation of cultured rat hepatic sinusoidal endothelial cells. Hepatology 22(3):969–973

    Article  CAS  PubMed  Google Scholar 

  27. Francescone RA 3rd, Faibish M, Shao R (2011) A Matrigel-based tube formation assay to assess the vasculogenic activity of tumor cells. J Vis Exp (55). https://doi.org/10.3791/3040

  28. Hendrix MJ, Seftor EA, Hess AR, Seftor RE (2003) Vasculogenic mimicry and tumour-cell plasticity: lessons from melanoma. Nat Rev Cancer 3(6):411–421. https://doi.org/10.1038/nrc1092

    Article  PubMed  CAS  Google Scholar 

  29. Nicosia RF (2009) The aortic ring model of angiogenesis: a quarter century of search and discovery. J Cell Mol Med 13(10):4113–4136. https://doi.org/10.1111/j.1582-4934.2009.00891.x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Schlaeger TM, Bartunkova S, Lawitts JA, Teichmann G, Risau W, Deutsch U, Sato TN (1997) Uniform vascular-endothelial-cell-specific gene expression in both embryonic and adult transgenic mice. Proc Natl Acad Sci U S A 94(7):3058–3063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nishida M, Carley WW, Gerritsen ME, Ellingsen O, Kelly RA, Smith TW (1993) Isolation and characterization of human and rat cardiac microvascular endothelial cells. Am J Phys 264(2 Pt 2):H639–H652

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, McGill University, Montreal, QC, Canada

    Huishi Toh & Andrew Bateman

  2. Centre for Translational Biology, Research Institute of McGill University, Montreal, QC, Canada

    Huishi Toh & Andrew Bateman

  3. Department of Anatomy, McGill University, Montreal, QC, Canada

    Eugene Daniels

Authors
  1. Huishi Toh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eugene Daniels
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew Bateman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrew Bateman .

Editor information

Editors and Affiliations

  1. Department of Medicine, McGill University MUHC, Montreal, Québec, Canada

    Andrew Bateman

  2. Department of Medicine, McGill University MUHC, Montreal, Québec, Canada

    Hugh P.J. Bennett

  3. Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China

    Siu Tim Cheung

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Toh, H., Daniels, E., Bateman, A. (2018). Methods to Investigate the Roles of Progranulin in Angiogenesis Using In Vitro Strategies and Transgenic Mouse Models. In: Bateman, A., Bennett, H., Cheung, S. (eds) Progranulin. Methods in Molecular Biology, vol 1806. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8559-3_22

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8559-3_22

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8557-9

  • Online ISBN: 978-1-4939-8559-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation